Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B

被引:144
作者
Su, GH
Chen, HM
Muthusamy, N
Garrett-Sinha, LA
Baunoch, D
Tenen, DG
Simon, MC [1 ]
机构
[1] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[3] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[5] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA
[6] Beth Israel Hosp, Div Hematol Oncol, Boston, MA 02115 USA
关键词
B cell antigen receptor; B lymphocytes; Ets factors; gene targeting; germinal centers;
D O I
10.1093/emboj/16.23.7118
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Spi-B is a hematopoietic-specific Ets family transcription factor closely related to PU.1. Previous gene targeting experiments have shown that PU.1 is essential for the production of both lymphocytes and monocytes. We have now generated mice with a null mutation at the Spi-B locus. Unlike PU.1 mutant mice, Spi-B-/- mice are viable, fertile and possess mature B and T lymphocytes. However, Spi-B-/- mice exhibit severe abnormalities in B cell function and selective T cell-dependent humoral immune responses, First, although Spi-B-/- splenic B cells respond normally to lipopolysaccharide stimulation in vitro, these B cells proliferate poorly and die in response to B cell receptor (surface IgM) cross-linking. Secondly, Spi-B-/- mice display abnormal T-dependent antigenic responses in vivo and produce low levels of antigen-specific IgG(1), IgG(2a) and IgG(2b) after immunization. Finally, Spi-B-/- mice show a dramatic defect in germinal center formation and maintenance. In contrast to wild-type animals, germinal centers in Spi-B-/- mice are smaller and short-lived with significantly increased numbers of apoptotic B cells, Taken together, these results demonstrate that Spi-B is essential for antigen-dependent expansion of B cells, T-dependent immune responses and maturation of normal germinal centers in vivo.
引用
收藏
页码:7118 / 7129
页数:12
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