FcRH1: an activation coreceptor on human B cells.
FcRH1: an activation coreceptor on human B cells.
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DOI：
10.1182/blood-2004-06-2344
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发表时间：
2004-10
期刊：
影响因子：
20.3
通讯作者：
C. Leu;R. Davis;L. Gartland;W. D. Fine;M. Cooper
中科院分区：
文献类型：
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作者：
C. Leu;R. Davis;L. Gartland;W. D. Fine;M. Cooper
B细胞活化和分化通过细胞表面受体的动态阵列的协调功能来调节。在其分化的不同阶段，人B细胞可表达具有调节潜力的免疫球蛋白Fc受体同源物（FcRH）大家族的一个或多个成员。在这些新鉴定的跨膜分子中，FcRH1是唯一的，在其胞内结构域中具有2个基于免疫受体酪氨酸的激活基序（ITAM）样基序。在这里，我们使用新的单克隆抗FcRH1抗体的Fab片段和mRNA分析来评估FcRH1在B细胞分化过程中的表达和功能。FcRH 1表达开始于前B细胞，在幼稚B细胞上达到峰值水平，并且在B细胞被激活以开始形成生发中心后下调。这种FcRH1下调与前生殖中心细胞的急剧扩大、细胞周期进入和其他明显的活化迹象（包括CD80和CD86上调和免疫球蛋白D（IgD）下调）相一致。体外分析表明，FcRH1的连接导致其酪氨酸磷酸化和适度的B细胞活化和增殖。伴随的FcRH1连接增强B细胞抗原受体（BCR）诱导的Ca（2+）动员和增殖。因此，FcRH 1具有作为B细胞上的活化辅助受体的潜力。
B-cell activation and differentiation is regulated through the coordinated function of a dynamic array of cell surface receptors. At different stages in their differentiation, human B cells may express one or more members of a large family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential. Among these newly identified transmembrane molecules, FcRH1 is unique in having 2 immunoreceptor tyrosine-based activation motif (ITAM)-like motifs in its intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1 antibodies and mRNA analysis to evaluate FcRH1 expression and function during B-cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels on naive B cells, and is down-regulated after B cells are activated to begin to form germinal centers. This FcRH1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry, and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)-induced Ca(2+) mobilization and proliferation. FcRH1 thus has the potential to serve as an activating coreceptor on B cells.