MOLECULAR-BASIS OF THE ALLELIC INHERITANCE OF RABBIT IMMUNOGLOBULIN VH ALLOTYPES - IMPLICATIONS FOR THE GENERATION OF ANTIBODY DIVERSITY

被引:177
作者
KNIGHT, KL
BECKER, RS
机构
[1] Department of Microbiology Stritch School, Medicine Loyola University Chicago, Maywood
基金
美国国家卫生研究院;
关键词
D O I
10.1016/0092-8674(90)90344-E
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
Rabbits are unique in that their immunoglobulin VH regions bear allotypic markers encoded by allelic genes. The presence of these markers on most serum immunoglobulins is difficult to explain, as the germline contains several hundred VH genes. We cloned VH genes from normal rabbits of the VHa allotypes a1, a2, and a3 and from a mutant a2 rabbit, Alicia, which expresses almost no a2 allotype. The D-proximal VH gene VH1 of normal rabbits encoded prototype a1, a2, or a3 allotype VH regions in a1, a2, or a3 rabbits, respectively; VH1 was shown to be preferentially utilized in leukemic rabbit B cells. This VH1 gene was deleted from the germline of the Alicia rabbit. These data suggest that the allelic inheritance of a allotypes results from preferential utilization of VH1 in VDJ rearrangements. We suggest that antibody diversity in rabbit primarily results from somatic hypermutation and gene conversion. © 1990.
引用
收藏
页码:963 / 970
页数:8
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