Aging-associated intrinsic defects in IgA production by murine Peyer's patch B cells stimulated by autoreactive Peyer's patch T cell hybridoma-derived B cell stimulatory factors (BSF).
Immune functions deteriorate with age, primarily as a result of alterations in the number and subpopulations of T cells of the immune system. In contrast, the B cell component of the immune system is generally affected by senescence only to a minor extent. In the present report, we stimulated murine Peyer's patch (PP) B cells by nonspecific multifunctional B cell stimulatory factors (BSF) secreted by one of several autoreactive (self-major histocompatibility complex (MHC)-class II antigen-responsive) T cell hybridoma clones derived from PP of syngeneic mature adult mice, and then determined in vitro whether aging-associated intrinsic defects could be demonstrated in the proliferation of, and the synthesis and secretion of mucosal IgA by, the BSF-activated B cells. This approach could be a useful new in vitro method for assessing the effect of senescence on B cell Ig production, especially that of IgA, in the gut-associated lymphoid tissue (GALT). Aged PP B cells stimulated by the autoreactive PP T cell-derived BSF proliferated more (P less than 0.05), contained larger amounts of IgA (nearly 10 times) and also secreted considerably more IgA (nearly 4.5 times) than did mature adult PP B cells. However, the ratio of intracellular dimeric (d) IgA to total IgA in the aged B cell lysates was significantly reduced (by approx. 44%) as was also the secreted dIgA (by approximately 50%). The augumentation of not only the proliferation, but also the synthesis and secretion of IgA in vitro along with reduced dIgA/total IgA ratios of BSF-stimulated aged PP B cells appears to be due to aging-related intrinsic defects. Alterations in intracellular regulatory mechanisms of B cells, mediated by B cell receptors for autoreactive T cell-derived BSF, could be largely responsible for the observed polyclonal B cell hyperreactivity, associated with senescence.
Kawanishi
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Gut Mucosal Immunity Lab., V.A.M.C., Northport and SUNY at Stony Brook 11768.
Senda
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Ajitsu
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D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D007071:Immunoglobulin A, Secretory; D007378:Interleukins; D015847:Interleukin-4