Pre-B cell loss in senescence coincides with preferential development of immature B cells characterized by partial activation and altered Vh repertoire.
Senescent mice show decline in B lymphopoiesis marked by reduced pre-B cells. Analysis of bone marrow from aged (approximately 2 years old) BALB/c mice indicates that, in senescence, an increased proportion of immature B cells exhibit a CD43/S7+ surface phenotype. This results from continued production of new CD43/S7+ B cells in aged mice from their limited pre-B cell pool while production of CD43/S7- immature B cells is highly reduced. CD43/S7 is ordinarily observed on a minor subset of immature B cells in young mice and is indicative of their partial activation. Senescent immature B cells, both ex vivo and derived in vitro, also demonstrate increased expression of VhS107 concomitant with CD43/S7. These alterations in the phenotype and Vh repertoire among senescent immature B cells likely originate prior to surface Ig expression. In aged mice with depleted pre-B and immature B cells in vivo, pre-B and immature B cells exhibited increased apoptosis in vitro. Dexamethasone-induced apoptosis among B lineage cells in young adult mice also resulted in pre-B cell loss and increased expression of CD43/S7 and VhS107 among immature B cells similar to that observed spontaneously in aged mice. These results suggest that old age, possibly due to increased apoptosis, results in loss of pre-B cells and alterations in the phenotype and Vh repertoire of newly derived B cells.
Wilson
Emily L
EL
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 (R138), Miami, FL 33101, USA.
King
Anne M
AM
Sherwood
Erin M
EM
Riley
Richard L
RL
D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D016130:Immunophenotyping; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012795:Sialoglycoproteins / Q000032:analysis
D015703:Antigens, CD; D005938:Glucocorticoids; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D003907:Dexamethasone