title: Impaired B lymphopoiesis in old age: a role for inflammatory B cells?
abstract: Continued generation of new B cells within the bone marrow is required throughout life. However, in old age, B lymphopoiesis is inhibited at multiple developmental stages from hematopoietic stem cells through the late stages of new B cell generation. While changes in B cell precursor subsets, as well as alterations in the supporting bone marrow microenvironment, in old age have been known for the last 20 years, only more recently have insights into the cellular and molecular mechanisms responsible become clarified. Our recent discovery that B cells in aged mice are pro-inflammatory and can diminish B cell generation within the bone marrow suggests a potential mechanism of inappropriate "B cell feedback" which contributes to a bone marrow microenvironment unfavorable to B lymphopoiesis. We hypothesize that the consequences of a pro-inflammatory microenvironment in old age are (1) reduced B cell generation and (2) alteration in the "read-out" of the antibody repertoire. Both of these likely ensue from reduced expression of the surrogate light chain (λ5 + VpreB) and consequently reduced expression of the pre-B cell receptor (preBCR), critical to pre-B cell expansion and Vh selection. In old age, B cell development may progressively be diverted into a preBCR-compromised pathway. These abnormalities in B lymphopoiesis likely contribute to the poor humoral immunity seen in old age.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, P.O. Box 016960 (R-138), Miami, FL, 33101, USA, rriley@med.miami.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Riley
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060833:Cellular Microenvironment / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis / Q000502:physiology*