title: Deviation of the B cell pathway in senescent mice is associated with reduced surrogate light chain expression and altered immature B cell generation, phenotype, and light chain expression.
abstract: B lymphopoiesis in aged mice is characterized by reduced B cell precursors and an altered Ab repertoire. This likely results, in part, from reduced surrogate L chains in senescent B cell precursors and compromised pre-BCR checkpoints. Herein, we show that aged mice maintain an ordinarily minor pool of early c-kit(+) pre-B cells, indicative of poor pre-BCR expression, even as pre-BCR competent early pre-B cells are significantly reduced. Therefore, in aged mice, B2 B lymphopoiesis shifts from dependency on pre-BCR expansion and selection to more pre-BCR-deficient pathways. B2 c-kit(+) 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 kappa L chain expression. Notably, immature B cells in aged bone marrow exhibit a similar phenotype in vivo. We hypothesize that reduced surrogate L chain expression contributes to decreased pre-B cells in aged mice. The B2 pathway is partially blocked with limited B cell development and reduced pre-BCR expression and signaling. In old age, B2 pathways have limited surrogate L chain and increasingly generate new B cells with altered phenotype and L chain expression.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alter-Wolf
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
authors.forename: Richard L
authors.initials: RL
authors.lastname: Riley
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D054444:Immunoglobulin Light Chains, Surrogate / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D016130:Immunophenotyping; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054420:Pre-B Cell Receptors / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D054444:Immunoglobulin Light Chains, Surrogate; D054420:Pre-B Cell Receptors