Profound reduction of mature B cell numbers, reactivities and serum Ig levels in mice which simultaneously carry the XID and CD40 deficiency genes

被引:44
作者
Oka, Y
Rolink, AG
Andersson, J
Kamanaka, M
Uchida, J
Yasui, T
Kishimoto, T
Kikutani, H
Melchers, F
机构
[1] BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND
[2] OSAKA UNIV,SCH MED,DEPT MED 3,SUITA,OSAKA 565,JAPAN
[3] UNIV UPPSALA,CTR BIOMED,DEPT IMMUNOL,S-75123 UPPSALA,SWEDEN
[4] OSAKA UNIV,INST MOL & CELLULAR BIOL,SUITA,OSAKA 565,JAPAN
关键词
D O I
10.1093/intimm/8.11.1675
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It has been known for some time that single mutant nude or CD40T mice have apparently normal numbers of cells in the precursor compartments of bone marrow and the mature B cell compartments of the periphery. X-linked immunodeficiency (XID) mice are deficient only in some of the slgM(+)slgD(+) B cells. We have investigated further the contributions of the rid mutation, of the T cell deficiency of nude and of the inability of CD40T a cells to cooperate with T cells in the generation of the precursor and the mature B cell compartments in mice. Double mutant XID/nu and XID/CD40T mice have precursor a cell compartments that are no more deficient than the single mutant XID mice. However, the peripheral a cell compartments of both XID/nu and XID/CD40T are even more deficient than those of single mutant XID mice. While 10% of the peripheral a cells of wild-type or CD40T, one-third of XID and half of XID/nu mice turn over rapidly, as many as three-quarters of those in XID/CD40T are short-lived. Total numbers of slgM(+)slgD(+) a cells in the spleen are at best 10-15% of normal mice at 6-8 weeks of age in XID, XID/nu and XID/CD40T mice. They remain that low at 3 months of age in XID/CD40T mice, while in XID mice these peripheral a cells slowly build up in numbers with age. As expected, double mutant XID/CD40T mice do not respond to the T-dependent antigen keyhole limpet hemocyanin. Only the responses to the T-independent type I antigen, TNP-lipopolysaccharide (LPS), appear to be normal. In vitro, their splenic B cells respond poorly to LPS or to IgM-specific antibody in either the absence or presence of cytokines. Most notably, serum IgM, IgG2b and lgG3 levels are severely depressed, while IgG1, IgG2a and IgA levels are <10 mu g/ml. The results suggest a model of mature a cell development in which the peripheral, mature B cell compartments are generated in two parallel, not tandemly organized pathways. They could be selected and/or stimulated at the transition from immature to mature a cells: in btk controlled or in CD40 controlled ways.
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页码:1675 / 1685
页数:11
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