Moreover, memory B cells have been detected early in the immune response, prior to the peak of the GC reaction [21, 23, 34, 36], suggesting that memory B cells emerge early from the GC or, alternatively, independently of GCs. To assess the relative contribution of GC-dependent and GC-independent pathways to memory B cell formation, an antigen-based cell-enrichment strategy was developed [20, 21]. Immunizing mice with the soluble protein phycoerythrin (PE), a fluorescent Td antigen, made

it possible to track PE-binding B cells in order to study memory and GC B cells. In this way, a precursor cell population was identified that could give rise to GC B cells and later differentiate into memory B or plasma cells. Early in the response and independently of the GC reaction, INCB018424 ic50 these precursors could differentiate

directly into memory B cells. The GC-independent memory B cells mainly retained IgM expression and were less mutated compared with the GC-derived memory B cells. In another model [23], conditional ablation LY2157299 supplier of Bcl-6, a transcription factor pivotal for the survival of GC B cells [39], was used to investigate the GC-dependent and GC-independent pathways in response to the Td antigen, NP-CGG, using IgG1+ NP-specific B cells as read-out [23]. Deletion of Bcl-6 in B cells did not affect B cell development per se whereas it did reduce the number of antigen-specific GC B cells after why immunization. However, antigen-specific memory B cells were still present, indicating that memory B cells develop

independently of GCs. There seems to be a difference although between memory B cells that develop in a GC-independent compared with GC-dependent manner with respect to SHM. Those that developed in a GC-independent manner did not show signs of SHM by contrast to the GC-dependent memory B cells. Early in the primary response, the GC-independent unmutated memory B cells undergo expansion to become long-lived cells that express antibodies with low affinity. As the response progresses, these cells become resting and are later joined by mutated GC progenies. Together these two populations comprise the memory B cell pool at comparable frequencies and mediate secondary antibody responses upon adoptive transfer. Moreover, and consistent with memory B cells expressing CD80, PDL-2 and CD73 [15], these markers were also detected on memory B cells in this study although not analysed in detail. Finally, it was suggested that the memory compartment is generated as two layers of cells: those uniquely tailored to the pathogen and those that are unmutated in order to accommodate cross-reacting specificities of related pathogens. TFH cells have been suggested as an essential cellular component for GC formation [5-8], and Bcl-6 is pivotal also for the differentiation of TFH cells [5]. In the study just discussed [23], Bcl-6 was conditionally deleted selectively in CD4-expressing cells.

In areas of high endemicity, the lifetime infection rate is above 50%, and more than 8% of the population are chronic carriers.5 Infection in such regions is typically acquired in childhood, either horizontally from other children or perinatally from maternal carriers. By contrast, parenteral transmission is common in Australia, and fewer than 2% of the population are chronic HBV carriers. Hepatocellular carcinoma is the sixth most common cancer worldwide, and half of all cases are caused by HBV.6 HBV is the second most important RGFP966 carcinogen after cigarette smoke. In dialysis units both patient-to-patient and patient-to-staff transmission of the virus have been recognized

since the 1960s. Before the advent of vaccination, FK506 some success in limiting the spread of HBV was achieved by dialysing seropositive patients separately from those who were seronegative. This followed the publication in the UK of the Rosenheim Report in 1972,7 which set out a code of practice for reducing transmission of hepatitis among dialysis patients. In 1977, guidelines were published in the USA to reduce HBV infection in dialysis units.8 The incidence of new hepatitis B infections in US dialysis patients subsequently fell from 6.2% in 1974 to 1% by 1980.9 Testing of a vaccine began in the 1970s,

and this came into widespread clinical use from the early 1980s.10,11 This further reduced the risk of HBV infection in the dialysis setting. Nevertheless, although rates of new infection are now low,12 hepatitis B continues to exist in dialysis populations. Prevalence

rates tend to be dependent on baseline population rates. An analysis of data from the Dialysis Outcomes and Practice Patterns Study showed an HBV prevalence of 0–6.6% across dialysis facilities in Western Europe, Japan and the USA.13 In contrast, a registry study of Asia–Pacific countries found the prevalence of hepatitis B surface antigen (HBsAg) positivity ranged between 1.3% and 14.6%.14 Reports from much smaller cohorts elsewhere have indicated HBsAg positivity rates of 13.3% in Turkey, and 2.4–10% next in Brazil.15–17 In addition to being at increased risk of infection, it has been demonstrated that HD patients are more likely to become chronic carriers of HBV than members of the general population.18 Patients with chronic kidney disease (CKD) have impaired host defences against viral infections.19 Consequently, risk of acquisition is increased in dialysis populations regardless of dialysis modality. Before the introduction of erythropoietin therapy, CKD patients were also at increased risk of infection via transfusion of contaminated blood products. The HD procedure presents the opportunity for blood contact with contaminated equipment, injection of liquids harbouring virus, and exposure of broken skin or mucous membranes to infection. HBV is particularly persistent in the environment, and may survive for more than a week on surrounding surfaces.

We recommend DRA be used in the future to more reliably model clinical avulsion injury. Avulsion is an injury with a chronic profile of degenerative and inflammatory progression,

and this theoretically provides a window of clinical therapeutic opportunity in treatment of secondary trauma progression. “
“This chapter contains sections titled: Introduction Functions of CSF and ISF in the CNS Physiology of CSF and ISF Composition of CSF During Health Considerations in Sampling and Analyzing CSF General Characteristics of CSF in Neurological Disease Recommendations for CSF Analysis in Neurotoxicity Evaluations References “
“Among epilepsy-associated Selleck TSA HDAC non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD), including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies, constituting about 50% of all surgical pathology of epilepsy. Several selleck chemicals distinct histological patterns have been historically recognized in both

HS and FCD, and several studies have tried to perform clinicopathological correlations. However, results have been controversial, particularly in terms of post-surgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future Phloretin clinicopathological studies. Meanwhile, we reviewed the neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation

of the distribution and severity of neuronal loss and gliosis within hippocampal formation, that is, HS type 1 (61%) equivalent to “classical” Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore, we performed a neuropathological comparative study on mTLE-HS and dementia-associated HS (d-HS) in the elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes, particularly Alzheimer type and TDP-43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated.

3a). T cell autoreactivity was accompanied by production of IFN-γ (GAD65) or IL-10 (IA-2) or both (insulin B9-23), possibly reflecting pathogenic as well as regulatory immune autoreactivity to islets [6]. The insulin A-chain (aa1-14) epitope, claimed recently to be recognized dominantly by T cells from pancreas-draining

lymph nodes of long-standing type 1 diabetes patients, was not yet known at the time of the patient’s death [10], and was therefore not tested. It is conceivable that pancreas-draining lymph nodes contain islet immune components that bear relevance to insulitis and islet destruction. Preliminary evidence of oligoclonality and reactivity to insulin peptide in two cases of long-standing type 1 diabetes exists [10]. The T cell response to insulin in that study was detected by IL-13 production in response to high doses click here selleck chemicals (in the millimolar

range) of insulin peptide, but not to whole insulin or proinsulin. In view of the lack of remaining β cells or insulitis in the latter donors, it remains unresolved whether the immune reactivity to insulin described is relevant to the disease onset. Given the clinical heterogeneity of type 1 diabetes, other candidate antigens such as GAD65, IA-2 or as yet unidentified β cell proteins should still be considered [16]. Our first case expressed an HLA genotype that does not particularly predispose to development of type 1 diabetes [20]. Diagnosis of this disease was, however, corroborated by the detection of autoantibodies against Amoxicillin GAD65 [21]. However, this patient presented unexpectedly with enteroviral infection of pancreatic β cells that may contribute to loss of immunological tolerance

and impaired β cell function [17]. Despite the presence of intact β cells and insulitis in our patient, it is not yet possible to determine the degree of representation of this case in defining immune responses that are associated with the onset of inflammatory lesions in the islets of genetically predisposed patients. Furthermore, studies were performed at a time that the patient’s blood glucose could be regulated by modest doses of exogenous insulin, implying that our patient was either in remission (‘honeymoon’) at the time of his accidental death, or suffering from a syndrome referred to as latent autoimmune diabetes in adults (LADA) [22]. There is no reason to believe that the pathology of LADA differs from type 1 diabetes in terms of disease mechanism and manifestation [23]. In fact, the low insulin requirement and good metabolic control were accompanied by islet autoreactivity composed of pro- as well as anti-inflammatory immune responses. We propose that the immune response described could bear relevance to disease regulation [6] similar to the pre-onset (peri-insulitis) stage in NOD mice.

Cilengitide treatment resulted in a significantly decreased diameter of the J3T-1 tumor vessel clusters and its core vessels when compared with controls, while an anti-invasive effect was shown in the J3T-2 glioma with a significant reduction of diffuse cell infiltration around the tumor center. The survival of cilengitide-treated mice harboring J3T-1 tumors was significantly longer than that of control animals (median survival: 57.5 days and 31.8 days, respectively, P < 0.005), while cilengitide had no effect on the survival of mice with J3T-2 tumors MI-503 manufacturer (median survival: 48.9

days and 48.5, P = 0.69). Our results indicate that cilengitide exerts a phenotypic anti-tumor effect by inhibiting angiogenesis and glioma cell invasion. These two mechanisms are clearly shown by the experimental treatment of two different animal invasive glioma models. “
“We studied a frontal lobe subcortical cystic tumor that had been resected from a 13-year-old girl with a 3-year history of intractable partial seizure. Currently, more than 13 years after surgery, the patient remains recurrence-free and has no neurological deficits. Histological examination showed that the tumor was non-infiltrating

and paucicellular with a mucinous matrix, PD184352 (CI-1040) and consisted of fairly uniform small cells with round ACP-196 solubility dmso to oval nuclei. Within the mucinous matrix, the tumor cells were often arranged in pseudorosettes around small blood vessels. Mitotic activity and necrosis were absent, with a Ki-67 labeling

index of <1%. Based on the immunohistochemical and ultrastructural findings, the constituent tumor cells were considered to be those of oligodendroglioma, including mini-gemistocytes and gliofibrillary oligodendrocytes. No neuronal elements were identified. Features of cortical dysplasia (FCD Type 1) were evident in the cortex covering the lesion. The surrounding white matter also contained a significant number of ectopic neurons. The entire pathological picture appeared to differ somewhat from that of ordinary oligodendroglioma (WHO grade II). Considering the clinical and pathological features, the present unusual oligodendroglioma appeared to represent a previously undescribed form of oligodendroglioma (WHO grade I) lying within the spectrum of dysembryoplastic neuroepithelial tumor (DNT; WHO grade I). Simultaneously, the present oligodendroglioma also raises the question of whether or not oligodendrocyte-like cells of DNTs truly show neurocytic differentiation. "
“J. Satoh, H. Tabunoki, T. Ishida, Y. Saito and K.

15,16 Recently, it has been shown that the recovery of GFR within 1 month of delivery is largely attributable to recovery of filtration capacity. Moran et al. were able to show that all elements of GFR control, that is, blood flow, surface area and transfer coefficients, are altered in preeclampsia17 and that changes in basement membrane size-selectively

are relevant to the development of proteinuria. The estimation and subsequent quantification of proteinuria GSK2118436 cell line remains a challenge in preeclampsia diagnosis. Much work has been done to validate a spot urine test of protein : creatinine ratio to establish a firm diagnosis of proteinuria18 compared with the clinical ‘gold standard’ of a 24 h urine collection for protein assessment. The threshold for abnormal protein excretion is increased to 300 mg per day, or 30 mg/mmol creatinine.19 This threshold is an all or none categorization of renal involvement as there has been no evidence that the foetal or maternal outcomes are directly related to the degree of proteinuria. In everyday clinical practice the spot test has the ease of collection but requires local validation; in some centres the protein creatinine ratio is still questioned in terms of reliability.20 In contrast to spot urinary protein : creatinine

ratios performed outside of pregnancy, during pregnancy there is a loss of the diurnal variation of protein excretion.21 The use of the 24 h test is fraught with Palbociclib chemical structure difficulties resulting in inaccuracies.22

In pregnancy the physiological dilatation of the ureters and incomplete bladder emptying as a result of the enlarging uterus can cause significant collection errors.18 These errors can be avoided by ensuring adequate hydration and standardization of the collection technique (discarding urine at the beginning of the collection and lying in left lateral recumbency for 45 min at the end of the collection to remove any partial obstruction related to supine or upright posture).18 The renin-angiotensin-aldosterone system (RAAS) has been investigated in preeclampsia. The normal physiological response of the RAAS in pregnancy is an increase in circulating renin, angiotensinogen, angiotensin II and aldosterone.7,23 Pregnant women are ADAMTS5 resistant to the pressor effects of angiotensin and despite these changes remain normotensive throughout pregnancy. In contrast, women with preeclampsia have normal or below normal levels of renin, aldosterone and angiotensin II.23–25 Despite these hormonal changes in women with preeclampsia, they paradoxically have a reduction in plasma volume.26 The decline in plasma volume occurs several weeks prior to the rise in blood pressure and the other clinical manifestations of preeclampsia. Despite the decline in plasma volume prior to the onset of disease, women who will develop preeclampsia do not salt waste but do demonstrate an exaggerated diuresis in response to sodium loading.

Case: An 80-year-old man with history of chronic obstructive lung disease, coronary artery disease, atrial fibrillation and complete heart block was admitted to our facility with AZD6738 clinical trial complaints of chills, confusion, nausea, vomiting, periodic loose stools and 10 lb weight loss over the past 3 weeks. A PPM had been placed 12 years prior to admission and the generator was changed 8 years ago. Warfarin therapy was underway. Examination revealed a thin man who was afebrile and appeared dehydrated. Lungs were clear on auscultation, cardiac examination revealed

a grade II/VI holosystolic murmur heard best at the lower left sternal border, the left pectoral pacemaker site did not appear inflamed and was non-tender, and the abdomen was soft and without organomegaly. There were no skin lesions, leg oedema or abnormal ocular findings. Laboratory and radiology studies showed the following: haemoglobin = 11.8 g dl−1, white blood cell count = 2600 dl−1, platelets – 77 000 mm−13, creatinine = 1.3 mg dl−1 and albumin =0> 3.1 g dl−1;

electrolytes and liver function tests were normal; urinalysis showed one white blood cell and nine red blood cells; chest radiograph was normal except for the presence of a pacemaker; electrocardiogram showed normal pacing and capturing; selleck kinase inhibitor cerebrospinal fluid showed no cells; and otherwise normal findings. Two separate sets of blood cultures revealed Candida parapsilosis. 4-Aminobutyrate aminotransferase Transoesophageal echocardiography revealed a 0.5 × 0.5 cm mobile mass on the pacemaker lead along with moderate tricuspid regurgitation and fibrous strands on the

tricuspid valve. The patient was given amphotericin B deoxycholate and he subsequently developed fever. A follow-up chest radiograph revealed a left lower lobe infiltrate and a spiral CT scan showed a large pulmonary embolus occupying the posterior left main pulmonary artery, which extended into the proximal left lower lobe pulmonary artery branches. The left lower lobe was partially infarcted. The pacemaker was subsequently explanted and its leads removed percutaneously. Cultures of the pacemaker vegetation and wire were positive for C. parapsilosis. Antifungal susceptibility testing was not carried out on this isolate. Amphotericin B was maintained for 3 weeks after pacemaker removal and the patient was clinically stable at 1-year postinfection clinical visit. An English language computer-based literature search was conducted and references pertaining to PPM and implantable cardioverter-defibrillator infections were reviewed. The reference lists in all articles examined were also reviewed for additional relevant studies. All cases of well-documented CRMD-associated endocarditis caused by Candida species were identified and are included in Table 1. Cases lacking detailed clinical information including a description of management and outcome were excluded.

In accordance with our data, Meek et al. recently reported the same maturation arrest at selleck kinase inhibitor the T/NK-progenitor cell level using a DLL-4 over-expressing stroma cell line 7. CD34+lineagenegCD10+CD24+ committed B-cell precursors were not generated in our OP9/N-DLL1 co-culture. Colony-forming assays showed that freshly thawed huCD34+ HSCs preferentially formed colony-forming units of granulocytes/macrophages (CFU-GM) but also

colony-forming units of erythrocytes (CFU-E) (Fig. 1D). CTLPs on day 15 had completely lost their CFU-E capacity but retained a minor CFU-GM-forming capability, resulting in more macrophage- than granulocyte-colonies (Fig. 1E). CTLPs from CB-CD34 HSCs maintained both CFU-E and -GM capacities; however, reduced by 90% compared with freshly thawed huCD34+ HSCs (Fig. 1D). Next, we tested the in vivo-differentiation potential of CTLPs in the immunodeficient NOD-scid IL2Rγnull mouse model. After sub-lethal irradiation, these mice generally show a stable engraftment of huCD34+ HSCs after 10 wk in all haematopoietic lineages (including T cells), which is superior to that of conventional NOD-scid mice 9. We transplanted 6-wk-old animals intravenously

with huCD34+ HSCs plus unsorted CTLPs from a haploidentical third-party donor. Control mice Selleck Pifithrin-�� received only CTLPs, only huCD34+ HSCs, or no cellular support after irradiation. Ancestry of engrafting cells could be deduced to huCD34+ HSCs or CTLPs according to their expression of HLA-B07 (CTLPs were from a HLA-B07+, huCD34+ HSCs from a HLA-B07−donor). All mice survived until day 28, however, in the irradiation control and in mice receiving only CTLPs no engraftment of huCD45+ cells Clomifene could be detected (Fig. 2A). This is in contrast

with the previous reports in which CTLPs alone showed at least a thymic repopulating capacity 6, 7. However, in these experiments, CTLPs were given intrahepatically into neonatal mice, which is quite different to our experimental setting. Our design resembles more closely a possible clinical application and makes haematopoietic or lymphoid re-constitution solely driven by CTLPs unlikely. In contrast with this, recipients of huCD34+ HSCs and huCD34+ HSCs/CTLPs showed high levels of huCD45+ engraftment in spleen, BM and thymus (Fig. 2B). Interestingly, descendants from CTLPs could be found in the lymphoid as well as in the myeloid and monocytic compartment of the BM (Supporting Information Fig. 2B), reflecting the CFU data and current models of lineage plasticity in lymphoid progenitors 10. CTLPs further developed downstream the T-cell developmental pathway. In bichimeric mice, 42% of CD45+HLA-B7+ spleen cells were CD5+CD7+, compared with 15% in the CD45+HLA-B7− fraction and 5% in the spleen of the huCD34+ HSC controls (Fig. 2A).

1 mm Na3VO4, 5 μm ZnCl2 to obtain whole cell lysate. Protein was quantified using a bicinchoninic acid protein assay kit (Pierce, Rockford, IL). Gradient sodium dodecyl sulphate –polyacrylamide gel electrophoresis gels (Pierce/Thermo Fisher Scientific, Rockford, IL) were loaded with 10 μg of protein

and transferred to polyvinylidene fluoride membranes (Millipore). Western blots were probed with mouse anti-human Blimp-1 (Novus, Littleton, CO), mouse anti-human AID (Cell Signaling Technology, Beverly, MA), rabbit anti-human Xbp-1 (Novus), rabbit anti-human Pax5 (Millipore, Billerica, MA), mouse anti-human actin control (Calbiochem/EMD Chemicals, Gibbstown, NJ) and anti-GAPDH selleck chemicals llc control (Calbiochem). Mdm2 antagonist Secondary antibody labelling was performed using horseradish peroxidase-conjugated goat anti-mouse or goat anti-rabbit antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA) after washing. Western blots were visualized by autoradiography after incubation with enhanced chemiluminescence (Perkin Elmer Life Sciences Inc., Boston, MA). Human peripheral blood B cells express Cox-2 upon activation and Cox-2 activity is necessary

for optimal production of IgM and IgG.11,12 To determine if Cox-2 selective inhibitors preferentially influence the production of certain human antibody isotypes, we assessed production of IgM, total IgG, IgG1, IgG2, IgG3 and IgG4 following a 7-day stimulation with CpG plus anti-IgM. Peripheral blood human B cells were treated with either SC-58125 or NS-398, both small molecule Cox-2 selective inhibitors. Production of IgM and total IgG was measured by ELISA (Fig. 1a,b), while IgG1, IgG2, IgG3 and IgG4 (Fig. 1c–f) isotypes were measured

using Luminex Montelukast Sodium technology. We observed a significant decrease in IgM, total IgG, IgG1, IgG2, IgG3 and IgG4 following treatment of B cells with SC-58125. NS-398 also significantly inhibited the production of IgM, total IgG, IgG1, IgG2 and IgG3. Treatment with NS-398 also reduced IgG4 production, although, not in a dose-dependent manner. Based on PGE2 production from isolated PBMC the concentrations of Cox-2 selective inhibitors used to attenuate antibody production are sufficient to significantly inhibit Cox-2 activity (Fig. 1g). These new data demonstrate that both SC-58125 and NS-398 significantly attenuated production of all isotypes, indicating that Cox-2 inhibitors do not selectively inhibit antibody isotype production. The global decrease in antibody production induced by Cox-2 inhibition could be a result of reduced B-cell viability or proliferation. Therefore, we measured the percentage of cells that excluded 7-AAD on days 2, 4 and 6 of culture. Neither SC-58125 (Fig. 2a) nor NS-398 (data not shown) significantly affected the viability of activated human B cells measured on any of these days.

Indeed the mature recirculating B-cell pool in C57BL/6 mice appeared to be retaining both highly hydrophobic and highly charged CDR-H3 sequences. We have previously shown that selection against these types

of sequences can be thwarted, to a certain extent, by forcing increased bone marrow production of charged or hydrophobic CDR-H3s [20]. In BALB/c mice, late selective steps appear to ameliorate the effect of the change in the repertoire by reducing the number of B cells that have reached the final maturation step in the bone marrow. This clearly does not occur in C57BL/6 mice, as evidenced by significant increase in hydrophobic CDR-H3-bearing sequences Trichostatin A cost in fraction F B cells as well as the inability of C57BL/6 IgHa.ΔD-iD mice to reduce the numbers of fraction F B cells with highly charged, arginine-enriched CDR-H3s when compared with BALB/c IgHa.ΔD-iD mice and wild-type controls (Fig. 8 and 9). This apparent inability to efficiently perform late-stage somatic, clonal selection against “disfavored” sequence occurs in parallel with the apparent inability of C57BL/6 wild-type mice to reduce the use of the VH81X gene segment in the transition from fraction E to fraction F. Differences in mechanism could include differences in receptor editing in fraction E, or differences in the consequences of antigen receptor

influenced signaling after exposure to antigen in the periphery. These and other mechanisms are currently being studied in our laboratory. Whether or not the PLX4032 in vitro difference in the outcome of late-stage selection is contributing to the increased propensity of C57BL/6 to produce potentially pathogenic auto-reactive antibodies [26] is unclear. However, as analogous to the comparison of the

auto-immune prone C57BL/6 strain to the auto-immune resistant BALB/c strain, previous studies comparing MRL mice to their sister, autoimmune-resistant C3H strain have demonstrated a similar lack of control in the auto-immune prone MRL strain [27]. In either case, it appears that while the Hydroxychloroquine molecular weight C57BL/6 VH7183 repertoire contains reduced diversity of CDR-H1 and CDR-H2 due to decreased numbers of functional VH gene segments, there is increased diversity of CDR-H3 due to altered patterns of somatic selection. This appears to permit mature, recirculating C57BL/6 B cells to create a subset of antibodies within their repertoire with antigen-binding sites that are considerably less common, and potentially even nonexistent, in mature, recirculating BALB/c B cells. The role of these differences in creating a propensity for self-reactivity or other alterations in the immune response is a focus of ongoing investigations in our laboratory. We obtained bone marrow from C57BL/6 mice with either a wild-type or ΔD-iD [19] DH locus.