Old mice retain bone marrow B1 progenitors, but lose B2 precursors, and exhibit altered immature B cell phenotype and light chain usage.
The bone marrow of old adult mice ( approximately 2 years old) has reduced B lymphopoiesis; however, whether the B1 pathway in adult bone marrow is also compromised in senescence is not known. Herein, we show that phenotypic (IgM(-)Lin(-)CD93(+)[AA4.1(+)] CD19(+)B220(low/-)) B1 progenitors are retained in old bone marrow even as B2 B cell precursors are reduced. Moreover, B1 progenitors from both young adult and old mice generated new B cells in vitro enriched for CD43 expression, likely due to their activation, and exhibited increased lambda light chain usage and diminished levels of kappa light chain expression. B1 progenitors were shown to have lower surrogate light chain (lambda5) protein levels than did B2 pro-B cells in young mice and these levels decreased in both B1 and B2 precursor pools in old age. These results indicate that the B1 B cell pathway persists during old age in contrast to the B2 pathway. Moreover, B1 B cell progenitors generated new B cells in the adult bone marrow that have distinct surface phenotype and light chain usage. This is associated with decreased surrogate light chain expression, a characteristic held in common by B1 progenitors as well as B2 precursors in old mice.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Sarah
S
Alter-Wolf
Bonnie B
BB
Blomberg
Richard L
RL
Riley
D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D054444:Immunoglobulin Light Chains, Surrogate / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D051917:Leukosialin / Q000032:analysis; D038041:Lymphopoiesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology*
D018941:Antigens, CD19; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D051917:Leukosialin; C497863:Spn protein, mouse; D017493:Leukocyte Common Antigens