A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens

Functional dissection of the cytoplasmic subregions of the interleukin-5 receptor α chain in growth and immunoglobulin G1 switch recombination of B cells

The interleukin-5 receptor α chain (IL-5Rα) is known to regulate the development and function of B cells and eosinophils. Although the functions of IL-5Rα cytoplasmic domain subregions have been studied extensively using cultured cell lines, this approach has limitations when studying the functions of distinct primary B-cell subpopulations and their responsiveness to IL-5. In the present study, we generated mice on an IL-5Rα null background, each expressing a mutant form of an IL-5Rα transgene ligated to a µ enhancer and VH promoter, either lacking the cytoplasmic DC3 region or substituting two proline residues for alanine (ApvA) in the membrane-proximal ppvp motif of the cytoplasmic domain. The ppvp motif, which mediates activation of JAK2/STAT5 and Btk, also contributes to c-fos, c-jun and c-myc expression. IL-5Rα null mutant mice showed impaired B-1-cell development, reduced serum immunoglobulin G3 (IgG3) and IgM, no IL-5-induced enhancement of B-cell proliferation and IL-5-induced switch recombination from the µ gene to γ1 gene; these were not recovered following the expression of the ApvA mutant. In contrast, absence of the DC3 region affected the IL-5-induced switch recombination from the µ to the γ1 gene and B-1-cell development, while IL-5-induced proliferation and IgM production were at levels similar to those of B cells expressing wild-type IL-5Rα transgene. The results clearly indicated that the ppvp motif and the DC3 region of IL-5Rα played distinct roles in B-cell proliferation and differentiation. Thus, this present approach offers new insights into the functions of the cytoplasmic subregions of IL-5Rα, in particular its carboxy-terminal region

Purification and Immune Phenotyping of B-1 Cells from Body Cavities of Mice.

B-1 cells are fetal-origin B lymphocytes with unique developmental and functional characteristics that can generate natural, polyreactive antibodies with important functions in tissue homeostasis and immune defense. While B-1 cell frequencies in bone marrow and secondary lymphoid tissues are low, relative high frequencies exist within peritoneal and pleural cavities of mice, including both CD5+ and CD5- B-1 cells. These cells represent B-1 reservoirs that, when activated, migrate to lymphoid tissues to secrete antibodies and/or cytokines. Here, we outline efficient methods for the extraction and magnetic isolation of CD5+ B-1 cells from the peritoneal and pleural cavities as well as the separation and phenotypic characterization of CD5+ and CD5- B-1 cells by flow cytometry

Mammography interval and breast cancer mortality in women over the age of 75

PURPOSE: To evaluate the relationship between mammography interval and breast cancer mortality among older women with breast cancer. METHODS: The study population included 1,914 women diagnosed with invasive breast cancer at age 75 or later during their participation in the Women’s Health Initiative, with an average follow-up of 4.4 years (3.1 SD). Cause of death was based on medical record review. Mammography interval was defined as the time between the last self-reported mammogram 7 or more months prior to diagnosis, and the date of diagnosis. Multivariable adjusted hazards ratios (HR) and 95% confidence intervals (CIs) for breast cancer mortality and all-cause mortality were computed from Cox proportional hazards analyses. RESULTS: Prior mammograms were reported by 73.0 % of women from 7 months to ≤ 2 year of diagnosis (referent group), 19.4% (> 2 – < 5 years), and 7.5% (≥5 years or no prior mammogram). Women with the longest vs. shortest intervals, had more poorly differentiated (28.5% vs. 22.7%), advanced stage (25.7% vs. 22.9%) and estrogen receptor negative tumors (20.9% vs. 13.1%). Compared to the referent group, women with intervals of > 2 – < 5 years or ≥ 5 years had an increased risk of breast cancer mortality (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.03–2.54) and (HR 2.80, 95% CI, 1.57–5.00) respectively, p trend = 0.0002. There was no significant relationship between mammography interval and other causes of death. CONCLUSIONS: These results suggest a continued role for screening mammography among women 75 years of age and older