Vora K A, Lentz V M, Monsell W, Rao S P, Mettus R, Toscani A, Reddy E P, Manser T
Kimmel Cancer Center and Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA 19107, USA.
J Immunol. 2001 Mar 1;166(5):3226-30. doi: 10.4049/jimmunol.166.5.3226.
Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb-deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.
原癌基因A-myb的表达局限于发育中的中枢神经系统、成年睾丸、妊娠后期的乳腺以及次级B细胞滤泡的生发中心。先前通过生成和分析A-myb缺陷小鼠,已证明A-myb在其中三个部位表达的功能相关性,这些小鼠表现出行为异常、雄性不育以及妊娠期间乳腺发育紊乱。相比之下,我们在此表明,在A-myb缺陷小鼠中,由T细胞依赖性抗原免疫驱动的生发中心反应以及抗体V基因体细胞超突变、亲和力成熟和重链类别转换的相关过程明显正常。尽管如此,这些小鼠表现出轻度的脾白髓发育不全和原发性血清抗体反应减弱,这表明尽管A-myb不直接参与记忆B细胞反应的调节,但它可能在增强外周B细胞存活或增殖能力方面发挥作用。