ISOTYPE COMMITMENT OF HUMAN B-CELLS THAT ARE TRANSFORMED BY EPSTEIN-BARR-VIRUS

ISOTYPE COMMITMENT OF HUMAN B-CELLS THAT ARE TRANSFORMED BY EPSTEIN-BARR-VIRUS
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DOI:
10.1002/eji.1830210132
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发表时间:
1991-01-01
影响因子:
5.4
通讯作者:
COOPER, MD
COOPER, MD
中科院分区:
医学3区
文献类型:
--
作者:
MIYAWAKI, T;BUTLER, JL;COOPER, MD

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EB病毒(EBV)可以转化预活化的B细胞亚群,从而促进其生长和分化为浆细胞。在IgM产生细胞的EBV转化克隆中,生产性等位基因上的重链恒定区(C(H))基因以种系构型固定,而在同种型转换克隆中,与表达的C(H)基因邻近的C(H)基因缺失。 为了更精确地定义EBV易感性B细胞,我们根据细胞表面IG(sIG)同种型对B细胞亚群进行分类,用EBV感染它们,并确定它们在转化后可以产生哪些同种型。 大多数前体的IgM产生浆细胞表达IgM和IgD在其表面上,而少数表达IgM单独。 一些产生IgG和IgA的细胞的B细胞前体也表达sIgM,但令人惊讶的是没有一个表达IgD。 这些产生IgG和伊加的前体细胞携带sIgM,以相对低的水平表达,而表达高水平sIgM的B细胞不能产生IgG和伊加。IgG和伊加浆细胞的所有前体在其细胞表面上表达这些同种型。 有趣的是,能够产生IgG 3和IgA 2亚类的前体B细胞可以基于细胞sIgM的存在或不存在而分别富集。 这些结果证实了EBV可转化B细胞的同种型预定型。 他们进一步表明,残留的IgM在IgG和IgA定型的B细胞前体的表面瞬时表达,而sIgD表达在通过C(H)基因缺失的同种型转换过程中较早地消失。
Epstein-Barr virus (EBV) can transform a subpopulation of preactivated B cells thus promoting their growth and differentiation into plasma cells. In EBV-transformed clones of IgM-producing cells, the heavy chain constant region (C(H)) genes on the productive allele are fixed in germ-line configuration, whereas in isotype-switched clones the C(H) genes proximal to the expressed C(H) gene are deleted. In order to define more precisely the EBV-susceptible B cells, we sorted subpopulations of B cells on the basis of their cell surface Ig (sIg) isotypes, infected them with EBV, and determined which isotypes they could produce following transformation. Most precursors of IgM-producing plasma cells expressed both IgM and IgD on their surface, while a minority expressed IgM alone. Some B cell precursors of IgG- and IgA-producing cells also expressed sIgM, but surprisingly none expressed IgD. These precursors of IgG and IgA producers, which bore sIgM, expressed it in relatively low levels, whereas B cells expressing high levels of sIgM were incapable of generating IgG and IgA producer. All of the precursors of IgG and IgA plasma cells expressed these isotypes on their cell surface. Interestingly, precursor B cells capable of producing the IgG3 and IgA2 subclasses could be respectively enriched on the basis of the presence or absence of cell sIgM. These results demonstrate the isotype precommitment of EBV-transformable B cells. They further suggest that residual IgM is transiently expressed on the surface of the IgG- and IgA-committed B cell precursors, whereas sIgD expression is extinguished earlier in the process of isotype switching via C(H) gene deletion.