Thorbecke G J, Amin A R, Tsiagbe V K
Department of Pathology, New York University School of Medicine, New York 10016.
FASEB J. 1994 Aug;8(11):832-40. doi: 10.1096/fasebj.8.11.8070632.
Germinal centers in lymphoid tissue are the sites of generation of memory B cells undergoing isotype switching and somatic mutation in their Ig genes. Their formation cannot be induced by stimuli other than immunogenic ones. It seems likely that in the function and possibly also in the formation of germinal centers, one important factor is the localization of immune complexes with fixed complement on the surface of follicular dendritic cells. CD4+ T cells, located primarily in the "apical light zones" of the centers, are necessary for germinal center formation. However, their exact role in the process needs clarification, as both cell to cell contact and cytokine production could be involved at different stages of the germinal center generation. These T cells are usually specific for the antigen inducing the germinal center, but they may sometimes respond to other surface components on the B cell surface. In view of the possible stimulatory role of CD4+ T cells in follicular center-derived lymphomas, the functional significance of these T cells in germinal center proliferation is important to unravel. The B cells in germinal centers proliferate extremely rapidly, especially those located in the "dark zones." Many of them undergo apoptosis, particularly in the "basal light zones." The microenvironment of these centers is well suited to the task of expanding and selecting memory B cells of high affinity for the inducing antigen. The interactions of the proliferating B cells with dendritic cells and T cells, unevenly distributed in the various zones of the germinal center, are thought to determine which cells deserve rescue from apoptosis and induction to differentiation into small resting memory B cells. The memory B cells that emerge from the germinal center bear sIg, usually of "switched" isotype, and exhibit somatic mutations in the variable regions of their rearranged Ig genes.
淋巴组织中的生发中心是记忆B细胞产生的场所，这些B细胞在其免疫球蛋白（Ig）基因中经历同种型转换和体细胞突变。除免疫原性刺激外，其他刺激无法诱导其形成。在生发中心的功能以及可能的形成过程中，一个重要因素似乎是免疫复合物与固定补体在滤泡树突状细胞表面的定位。主要位于生发中心“顶部亮区”的CD4 + T细胞对于生发中心的形成是必需的。然而，它们在这一过程中的确切作用尚需阐明，因为细胞间接触和细胞因子产生可能参与生发中心形成的不同阶段。这些T细胞通常对诱导生发中心形成的抗原具有特异性，但它们有时也可能对B细胞表面的其他表面成分作出反应。鉴于CD4 + T细胞在滤泡中心来源淋巴瘤中可能具有的刺激作用，阐明这些T细胞在生发中心增殖中的功能意义非常重要。生发中心的B细胞增殖极其迅速，尤其是位于“暗区”的那些细胞。其中许多细胞会经历凋亡，特别是在“基底亮区”。这些生发中心的微环境非常适合扩增和选择对诱导抗原具有高亲和力的记忆B细胞。增殖的B细胞与在生发中心不同区域分布不均的树突状细胞和T细胞之间的相互作用，被认为决定了哪些细胞值得从凋亡中拯救出来，并诱导分化为静止的小记忆B细胞。从生发中心产生的记忆B细胞带有表面免疫球蛋白（sIg），通常是“转换”后的同种型，并在其重排的Ig基因可变区表现出体细胞突变。
