Rogerson B J
Trudeau Institute, Inc., Saranac Lake, NY 12983, USA.
Int Immunol. 1995 Aug;7(8):1225-35. doi: 10.1093/intimm/7.8.1225.
Murine B cells proliferating in the germinal centers of peripheral lymphoid tissue accumulate mutations in their rearranged variable regions, a diversification process which contributes to affinity maturation of the antibody response. The highly targeted nature of the hypermutation process could be explained by a somatic gene conversion mechanism. Well characterized examples of such an activity in B cells are seen during diversification of the chicken and rabbit Ig repertoires. The genomic organization, low complexity and high degree of homology exhibited by the four members of the murine VHS107 gene family suggested that these gene segments may be suitable candidates for the search of gene conversion events derived from upstream VHS107 counterparts. After an immune response to a complex T cell-dependent antigen (sheep red blood cells), rearranged V13, V11 and V1 genes were isolated from splenic extrafollicular and germinal center B cells. Extensive somatic mutation was evident in V11 and V1 sequences. When these sequences were examined, as well as V1 sequences isolated from phosphorylcholine-specific hybridomas, the observed nucleotide changes were not associated with any gene conversion between family members, suggesting instead that they arose by a mechanism which introduces point mutations.
在外周淋巴组织生发中心增殖的小鼠B细胞，其重排的可变区会积累突变，这一多样化过程有助于抗体应答的亲和力成熟。高突变过程的高度靶向性可以通过体细胞基因转换机制来解释。在鸡和兔Ig库多样化过程中可以看到B细胞中这种活性的典型例子。小鼠VHS107基因家族的四个成员所表现出的基因组组织、低复杂性和高度同源性表明，这些基因片段可能是寻找源自上游VHS107对应物的基因转换事件的合适候选者。在对复杂的T细胞依赖性抗原（绵羊红细胞）产生免疫应答后，从脾脏滤泡外和生发中心B细胞中分离出重排的V13、V11和V1基因。V11和V1序列中明显存在广泛的体细胞突变。当检查这些序列以及从磷酸胆碱特异性杂交瘤中分离出的V1序列时，观察到的核苷酸变化与家族成员之间的任何基因转换均无关，相反表明它们是由引入点突变的机制产生的。
