Linton P J, Rudie A, Klinman N R
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
J Immunol. 1991 Jun 15;146(12):4099-104.
Newly generating memory B cells rapidly accumulate somatic mutations that can alter their Ag-combining sites and potentially engender recognition of self determinants. To investigate the possibility that, during their emergence secondary B cells pass through a window of tolerance susceptibility, we have examined the in vitro generation of memory B cells in the presence or absence of tolerogen. The findings indicate that, before antigenic stimulation, precursors to memory B cells are resistant to tolerance induction. However, 2 to 7 days after T cell-dependent antigenic stimulation, newly emerging hapten-specific secondary B cells can be inactivated by the presence of hapten on a carrier not recognized by available Th cells. This inactivation can be blocked by the presence of free hapten and can be competed by the presence of immunogen. Inactivation of newly generating secondary B cells appears less specific than the tolerance induction of immature neonatal or bone marrow B cells because inactivation can be accomplished by cross-reactive determinants. Interestingly, the presence of tolerogen after primary stimulation did not preclude the generation of cells responsive to a third in vitro stimulation. Therefore, whereas newly emerging memory B cells are highly susceptible to inactivation, the progression of the clones of progenitors to memory B cells appears resistant to tolerance induction.
新产生的记忆B细胞会迅速积累体细胞突变，这些突变可改变其抗原结合位点，并可能导致对自身决定簇的识别。为了研究在次级B细胞出现过程中，它们是否会经历一个耐受易感窗口，我们检测了在有或没有耐受原存在的情况下记忆B细胞的体外生成情况。研究结果表明，在抗原刺激之前，记忆B细胞的前体细胞对耐受诱导具有抗性。然而，在T细胞依赖性抗原刺激后的2至7天，新出现的半抗原特异性次级B细胞会被载体上存在的、未被可用Th细胞识别的半抗原所灭活。这种灭活可被游离半抗原的存在所阻断，并可被免疫原的存在所竞争。新产生的次级B细胞的灭活似乎不如未成熟新生或骨髓B细胞的耐受诱导那么特异，因为灭活可通过交叉反应决定簇来完成。有趣的是，初次刺激后耐受原的存在并不排除产生对第三次体外刺激有反应的细胞。因此，虽然新出现的记忆B细胞极易被灭活，但祖细胞克隆向记忆B细胞的进展似乎对耐受诱导具有抗性。
