Biology of germinal centers in lymphoid tissue

Abstract

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.

Scrapie-Specific Pathology of Sheep Lymphoid Tissues

“…Immune stimulation of primary follicles leads to the development of germinal centre-containing secondary follicles as a result of the deposition of antigen/antibody complexes on the surface of FDCs. This stimulates the development of extended dendritic networks associated with mature FDCs as demonstrated by immunoglobulin labelling [23]. Our results show that in regressing follicles of both scrapie affected and control sheep, immunoglobulin labelling is lacking and exosome-like structures are found in place of electron dense material between FDC dendrites.…”

Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking theestrogen receptor alphagene

“…The GC may be an important site of immune dysregulation and disruption of B cell tolerance in autoimmune diseases (7)(8)(9). GC formation occurs in mice that spontaneously develop autoimmunity (10-12).…”

“…Germinal centers (GCs) are sites of Ig class switch, Ig gene V-region somatic hypermutations, and B cell tolerization and are thought to be an important site of immune dysregulation in autoimmune disease (7)(8)(9). In NZB ϫ NZW F1 mice (10), a well-characterized model of autoimmunity in mice, GC formation occurs in the absence of antigen challenge (10)(11)(12).…”

Malignancies in HIV/AIDS

“…In contrast, patients with BL and HL are usually diagnosed with somewhat higher CD4+ T cell counts [35, 54, 75]. CD4+ T cells modulate B cells and antibodies directed at extracellular organisms, and cell-mediated responses, which involve CD8+ T cell defense against intercellular organisms [76-81]. HIV can readily infect these CD4+ T cells and without HAART, they are destined to be depleted [76, 79].…”