GSBS Student Publications

Title

Regulation of B cell survival in xid mice by the proto-oncogene bcl-2

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology; Department of Physiology

Date

3-15-1996

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Anti-Idiotypic; Apoptosis; B-Lymphocytes; Cell Survival; Female; Hypergammaglobulinemia; Immunologic Deficiency Syndromes; Lymphopenia; Male; Mice; Mice, Inbred A; Mice, Inbred CBA; Mice, Mutant Strains; Mice, Transgenic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes; Suppressor Factors, Immunologic; Transgenes; X Chromosome

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

CBA/N mice carry an X-linked immunodeficiency (xid) due to a point mutation in the Bruton's tyrosine kinase (btk) gene. xid mice have a smaller peripheral B cell pool than normal animals, lack CD5+ B cells (B1), and are hyporesponsive to mitogenic anti-Igs and thymus-independent type 2 Ags. The proto-oncogene bcl-2 affects B cell homeostasis by suppressing programmed cell death. We hypothesized that reduced bcl-2 expression could enhance programmed cell death in xid B cells, directly causing poor peripheral B cell survival and indirectly affecting Ag responsiveness. We measured and compared levels of endogenous Bcl-2 protein and spontaneous apoptosis in xid and normal B cells, and determined the effect of a human bcl-2/Ig minigene on B cell survival and Ag responsiveness in bcl-2 transgenics. The amount of endogenous Bcl-2 was reduced fivefold in freshly isolated xid B cells compared with that in normal cells, but was equal in xid and normal T cells. Attrition by spontaneous apoptosis was significantly higher in cultured xid B cells. Expression of the bcl-2 transgene suppressed apoptosis equally in normal and xid B cells, prolonged in vitro survival, and markedly expanded in vivo the follicular B cell population normally reduced in xid mice. However, most xid defects persisted; xid/bcl-2 mice remained deficient in B1 cells and hyporesponsive to anti-Igs, thymus-independent type 1 Ags, and thymus-independent type 2 Ags. The data suggest that signal transduction pathways using Btk independently regulate B cell survival and Ag responsiveness.

Rights and Permissions

Citation: J Immunol. 1996 Mar 15;156(6):2143-54.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

8690903