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Development and Function of the Early B Cell Repertoire

 

作者: KearneyJohn E.,   BartelsJoachim,   HamiltonAnn Marie,   LehuenAgnès,   SolvasonNanette,   VakilMeenal,  

 

期刊: International Reviews of Immunology  (Taylor Available online 1992)
卷期: Volume 8, issue 2-3  

页码: 247-257

 

ISSN:0883-0185

 

年代: 1992

 

DOI:10.3109/08830189209055577

 

出版商: Taylor&Francis

 

关键词: idiotypes;CD5 B cell;amentum;connectivity;VH81X;thymocyte

 

数据来源: Taylor

 

摘要:

The early B cell repertoire is characterized by extensive interconnectivity, autoreactivity and multispecificity. Our preliminary sequence analysis of some of the idiotype specific antibodies is beginning to provide molecular clues to explain the observed multireactivity and the expression of shared idiotypic determinants on immunoglobulins of early B cells. The VHgene rearrangements analyzed are typical of the early pre-B cell and CD5 B cell repertoire. Some of these include shared or identical CDR3 regions resulting from the use of germline VH, D and JHgene segments in the absence of N region addition. As previously described, the most D proximal VHgenes are also used most frequently. Collectively these genetic restrictions, together with the lack of somatic mutation, suggest that the characteristic self reactivity of the early B cell repertoire is related to the expression of germline gene segments and limited use of diversification mechanisms. It has also been possible for the first time to isolate hybridomas secreting functional IgM molecules which use the most D proximal VHgene, VH81X. These antibodies and another example from theH7183 family have a broad multireactivity pattern possibly because of the presence of an unusually high number of charged amino acid groups present in the VHregion. These findings are preliminary and more extensive studies are needed to establish if these groups are responsible for the highly cross-reactive nature of these antibodies. Nevertheless, these unusual characteristics signify a unique role for antibodies expressing this VHgene during B cell development. It is also clear that the observed anti-lymphocyte reactivity, another feature of the newborn repertoire, is the result of the prevalence of B cells using similar if not identical VHDJHgenes and DJHjoins. The development of these B cells appears to occur consistently in early ontogeny and, again, are not found in conventional splenic B cells obtained from the normal adult. Understanding the functional significance of the early appearance of these antibodies may help to clarify and understand their role during development as well as in autoimmunity.We propose that the unique self reactive nature of the early repertoire provides a pattern within which self-assertiveness develops and results in the establishment of the adult repertoire. In doing so, dominant clones are established which may or may not be within, but whose selection and differentiation is directed by the CD5 B cell subset. Further understanding of how these interactions occur will come only from deeper understanding of the molecular nature of these receptors and their target self or non-self antigens.

 

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