Abstract
B lymphopoiesis in aged mice is characterized by reduced B cell precursors and an altered antibody repertoire. This likely results, in part, from reduced surrogate light chains in senescent B cell precursors and compromised preBCR checkpoints. Herein, we show that aged mice maintain an ordinarily minor pool of early c-kit
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pre-B cells, indicative of poor preBCR expression, even as preBCR competent early pre-B cells are significantly reduced. Therefore, in aged mice, B2 B lymphopoiesis shifts from dependency on preBCR expansion and selection to more preBCR deficient pathways. B2 c-kit
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B cell precursors, from either young or aged mice, generate new B cells in vitro that are biased to larger size, higher levels of CD43, and decreased κ light chain expression. Notably, immature B cells in aged bone marrow exhibit a similar phenotype in vivo. We hypothesize that reduced surrogate light chain expression contributes to decreased pre-B cells in aged mice. The B2 pathway is partially blocked with limited B cell development and reduced preBCR expression and signaling. In old age, B2 pathways have limited surrogate light chain and increasingly generate new B cells with altered phenotype and light chain expression.
