Developmental regulation of the human antibody repertoire.
Developmental regulation of the human antibody repertoire.
复制标题
人类抗体库的发育调节。
DOI：
10.1111/j.1749-6632.1995.tb55834.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Bertrand3rd,FE
中科院分区：
文献类型：
--
作者：
SchroederJr,HW;Mortari,F;Shiokawa,S;Kirkham,PM;Elgavish,RA;Bertrand3rd,FE
The ability to respond to antigen develops in a programmed fashion during ontogeny. In human," fetal" immunoglobulin gene segment utilization appears biased towards a small set of evolutionarily conserved V gene segments. Many of these gene segments are also used in antibodies with antigen specificities that do not arise until after infancy. The human fetus primarily regulates the diversity of the antibody repertoire through control of the H (heavy) chain CDR 3, which is generated by VDJ joining and forms the center of the antigen-binding site. Molecular modeling suggests that limitations in the length and composition of fetal CDR 3 intervals result in antibodies that contain a relatively" flat" antigen-binding surface that could serve to maximize the number of different interactions possible between the antibody and potential antigens. We propose that these limitations in the sequence and structure of H chain CDR 3 contribute to the low affinity and multireactivity of fetal antibody repertoires. The specific mechanisms used to generate a restricted fetal repertoire appear to differ between human and mouse. Nevertheless, included in the final products of both human and mouse fetal B cells will be antibodies that are quite homologous in composition and structure. The precise role that these antibodies play in the development of immunocompetence remains to be elucidated.
