Disrupted B-lymphocyte development and survival in interleukin-2-deficient mice.
Interleukin-2-deficient (IL-2-/-) mice develop a spontaneous, progressive, CD4+ T-cell-mediated colitis with an age-related decrease in the number of B lymphocytes. The aim of this study was to determine the mechanisms of B-cell loss in IL-2-/- mice. Serum immunoglobulin G1 (IgG1) levels in 8-week-old IL-2-/- mice were above normal but then decreased dramatically with advancing age. Between 8 and 11 weeks of age, the number of B-cell progenitors (B220+ IgM-) in the bone marrow of IL-2-/- mice was less than half of those in IL-2+/+ littermates. By 22 weeks of age, very few progenitor cells remained in the bone marrow of most mice, and spleens were almost devoid of B cells. Likewise, B1 cells were not present in the peritoneal cavity of aged IL-2-/- mice. Flow cytometry analysis of B-cell differentiation in the bone marrow suggested a progressive loss of B cells from the most mature to the least mature stages, which was not dependent on IL-2 receptor-alpha (IL-2Ralpha) expression. B cells transferred from normal animals had similar survival rates in IL-2-/- and wild-type mice. We conclude that conventional B cells in older IL-2-/- mice are lost by attrition owing to a derangement in B-cell development. Because B1 cells are less dependent on the bone marrow, a separate mechanism for their loss is suggested.
Schultz
M
M
Center for Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Clarke
S H
SH
Arnold
L W
LW
Sartor
R B
RB
Tonkonogy
S L
SL
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D007074:Immunoglobulin G; D007376:Interleukin-2