Loss of Bim allows precursor B cell survival but not precursor B cell differentiation in the absence of interleukin 7.
Interleukin (IL)-7 is a stromal cell-derived cytokine required for the survival, proliferation, and differentiation of B cell precursors. Members of the Bcl-2 family of proteins are known to have profound effects on lymphocyte survival, but not lymphocyte differentiation. To distinguish the relative dependence on IL-7 of B cell precursor survival versus B cell differentiation, the combined effects of lack of IL-7 and lack of the proapoptotic Bcl-2 relative, Bim, were studied. Bim is expressed to varying degrees in all B cell precursors and B cells. Lack of Bim compensated for lack of IL-7 in the survival of pro-, pre-, and immature B cells; however, lack of Bim did not substitute for the requirement for IL-7 in B cell precursor differentiation or B cell precursor proliferation. Precursor B cell survival is more dependent on sufficient levels of IL-7 than precursor B cell differentiation because the number of B cells and their precursors were reduced by half in mice heterozygous for IL-7 expression, but were restored to normal numbers in mice also lacking Bim. Hence, Bim and IL-7 work together to control the survival of B cell precursors and the number of B cells that exist in animals.
Oliver
Paula M
PM
Howard Hughes Medical Institute, Dept. of Immunology, 1400 Jackson St., Denver, CO 80206, USA.
Wang
Michael
M
Zhu
Yanan
Y
White
Janice
J
Kappler
John
J
Marrack
Philippa
P
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D000072224:Bcl-2-Like Protein 11; D001854:Bone Marrow Cells / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D005452:Fluoresceins; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D005452:Fluoresceins; D015851:Interleukin-7; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D013388:Succinimides