Memory B cells and the antibodies they encode are important for protective immunity against infectious pathogens. Characterization of naïve and memory B cell antibody repertoires will elucidate the molecular basis for the generation of antibody diversity in human B cells and the optimization of antibody structures that bind microbial antigens. In this study we aimed to investigate the influence of antigenic selection on the antibody genes of the two CD27 + memory B cell subsets, comparing them with the naïve repertoire in CD27 − cells. We analyzed and compared the Ig heavy chain gene transcripts in three recently defined circulating naïve and memory B cell subsets
SummaryDiminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses.
Keywords: B cells; chemokines, interleukins; human studies; neonatalAbbreviations: FACS, fluorescence activated cell sorting; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IL-4Ra, interleukin-4 receptor alpha chain; IL-13Ra1, interleukine-13 receptor alpha-1 chain; IRS-2, insulin receptor substrate 2; PBMCs, peripheral blood mononuclear cells; STAT6, signal transducer and activator of transcription 6; T1 B cell, transitional type 1 B cell.
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