The Journal of Experimental Medicine
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Published 1 November 2004. doi:10.1084/jem.20041129
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1179-1187
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Loss of Bim Allows Precursor B Cell Survival But Not Precursor B Cell Differentiation in the Absence of Interleukin 7

Paula M. Oliver1, Michael Wang2, Yanan Zhu5, Janice White1, John Kappler1,3,4, and Philippa Marrack1,3,5

1 Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center
2 Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80206
3 Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80206
4 Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80206
5 Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80206

Address correspondence to Philippa Marrack, Howard Hughes Medical Institute, Dept. of Immunology, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1324; Fax: (303) 398-1396; email: marrackp{at}njc.org

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.

Key Words: Bim • B cell development • IL-7 • B cell survival • Bcl-2 family

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; CLP, common lymphoid precursor; TSLP, thymic stromal lymphopoetin.


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