Mansikka A, Jalkanen S, Sandberg M, Granfors K, Lassila O, Toivanen P
Department of Medical Microbiology, Turku University, Finland.
J Immunol. 1990 Dec 1;145(11):3601-9.
Chickens that have been surgically bursectomized at 60 h of embryonic development usually generate Ig producing B cells; however, the bursectomized chickens are incapable of specific antibody responses, even after repeated immunization. In the present work, we analyzed the molecular basis of this immunodeficiency. In the bursectomized chickens, DNA sequencing revealed a repertoire of Ig L and H chains with a low number of different V-J and V-D-J joints, indicating an oligoclonal B cell compartment. In addition, the L and H chains belonging to each B cell clone had similar gene conversion events in the V region. In situ hybridization to Harderian gland tissue sections showed, that B cells of the bursectomized chickens were, however, capable of terminal plasma cell maturation. Thus, in chickens that were lacking the bursal microenvironment, 1) only a few B cell precursors differentiated into mature Ig-producing B cells, 2) low rate of gene conversion resulted in restricted Ig diversity. Regarding the chicken B cell differentiation, the present data support a model that the induction of B cell differentiation is a bursa-independent event, whereas the bursa of Fabricius has a crucial role in the amplification and diversification of the embryonic B cell repertoire.
在胚胎发育60小时时接受外科法氏囊切除的鸡通常会产生产生Ig的B细胞;然而,即使经过反复免疫,法氏囊切除的鸡也无法产生特异性抗体反应。在本研究中,我们分析了这种免疫缺陷的分子基础。在法氏囊切除的鸡中,DNA测序显示Ig轻链和重链的库中不同V-J和V-D-J连接的数量较少,表明B细胞区室为寡克隆。此外,属于每个B细胞克隆的轻链和重链在V区具有相似的基因转换事件。对哈氏腺组织切片进行原位杂交显示,法氏囊切除的鸡的B细胞能够进行终末浆细胞成熟。因此,在缺乏法氏囊微环境的鸡中,1)只有少数B细胞前体分化为成熟的产生Ig的B细胞,2)基因转换率低导致Ig多样性受限。关于鸡B细胞分化,目前的数据支持一种模型,即B细胞分化的诱导是一个不依赖法氏囊的事件,而法氏囊在胚胎B细胞库的扩增和多样化中起关键作用。