Pike Kelly A, Baig Ehtesham, Ratcliffe Michael J H
Department of Immunology, University of Toronto,Toronto, Ontario, Canada.
Immunol Rev. 2004 Feb;197:10-25. doi: 10.1111/j.0105-2896.2004.0111.x.
The bursa of Fabricius has evolved in birds as a gut-associated site of B-cell lymphopoiesis that is segregated from the development of other hematopoietic lineages. Despite differences in the developmental progression of chicken as compared to murine B-cell lymphopoiesis, cell-surface immunoglobulin (sIg) expression has been conserved in birds as an essential checkpoint in B-cell development. B-cell precursors that express an sIg complex that includes the evolutionarily conserved Igalpha/beta heterodimer colonize lymphoid follicles in the bursa, whereas B-cell precursors that fail to express sIg due to non-productive V(D)J recombination are eliminated. Productive retroviral gene transfer has allowed us to introduce chimeric receptor constructs into developing B-cell precursors in vivo. Chimeric proteins comprising the extracellular and transmembrane regions of murine CD8alpha fused to the cytoplasmic domain of chicken Igalpha efficiently supported B-cell development in precursors that lacked endogenous sIg expression. By contrast, expression of an equivalent chimeric receptor containing the cytoplasmic domain of Igbeta actively inhibited B-cell development. Consequently, the cytoplasmic domains of Igalpha and Igbeta play functionally distinct roles in chicken B-cell development.
法氏囊在鸟类中已演变为与肠道相关的B细胞淋巴细胞生成部位，该部位与其他造血谱系的发育相分离。尽管与小鼠B细胞淋巴细胞生成相比，鸡的发育进程存在差异，但细胞表面免疫球蛋白（sIg）表达在鸟类中作为B细胞发育的一个重要检查点得以保留。表达包含进化上保守的Igalpha/beta异二聚体的sIg复合物的B细胞前体定殖于法氏囊的淋巴滤泡中，而由于无效V(D)J重组而未能表达sIg的B细胞前体则被清除。高效逆转录病毒基因转移使我们能够在体内将嵌合受体构建体引入发育中的B细胞前体。由与鸡Igalpha的胞质结构域融合的小鼠CD8alpha的细胞外和跨膜区域组成的嵌合蛋白有效地支持了缺乏内源性sIg表达的前体中的B细胞发育。相比之下，含有Igbeta胞质结构域的等效嵌合受体的表达则积极抑制B细胞发育。因此，Igalpha和Igbeta的胞质结构域在鸡B细胞发育中发挥着功能上不同的作用。
