Functional anatomy of germinal centers

Abstract

This year we celebrate the first centennial of the discovery of germinal centers by Flemming in 1884. The present paper reviews and adds new data to the functional anatomy of a germinal center. Emphasizing its reactive nature, we first describe a germinal center reaction and then deal with its infrastructural aspects and constituent cell populations, both lymphoid and nonlymphoid. Elements involved in the de novo formation of a germinal center, like antigen, T cells, and the mysterious germinal-center-precursor cell, are discussed. Next, attention is paid to the requirements for lymphoid cells to migrate into germinal centers, and novel features of germinal-center-seeking cells are presented. Subsequently, we discuss kinetic aspects of the high proliferative activity in a germinal center; and finally a description of the functional capacities of germinal-center-derived cells, such as B memory cells and IgM-antibody-forming cell precursors, completes this picture of present-day knowledge of the germinal center, a structure which has yet to reveal its last secrets.

Altered Regulation of FcγRII on Aged Follicular Dendritic Cells Correlates with Immunoreceptor Tyrosine-Based Inhibition Motif Signaling in B Cells and Reduced Germinal Center Formation

“…Humoral responses exhibiting high levels of high affinity Ab to T-dependent Ags require not only T and B cells but also FDCs (31)(32)(33)(34)(35). In the present study, we compared the expression of surface receptors (i.e., Fc␥RII, and CR1/2) on young and old FDCs that is critical for IC retention and is involved in FDC-B cell interactions (5-7, 10 -17).…”

Textbook Germinal Centers?

“…However, past observations that GC formation may precede evident IC trapping by FDCs in certain situations cast the first doubt on this idea (1,23). This suspicion has been reinforced by recent studies on mice deficient in the ability to produce secreted Ab (and thus ICs) demonstrating that GC formation and at least the first stages of BCR hypermutation and affinity-based selection can occur in the absence of detectable levels of Ag on primary and secondary FDCs (24).…”

“…N early twenty years ago, the work of two factions of immunologists studying Ag-driven B cell responses using either serological and histological, or molecular genetic and hybridoma techniques coalesced (1)(2)(3)(4)(5)(6)(7)(8). Collectively, their findings implicated germinal centers (GCs) 3 as the principal sites in which the many steps of memory B cell development occur.…”

Seeing is believing: A focus on the contribution of microscopic imaging to our understanding of immune system function

“…The first phase of GC formation involves extensive proliferation [66], which occurs at the basal end of the FDC network close to the T cell zone [67]. Around day 10 after immunization, two distinct compartments of the GC (as identified using formalin-fixed tissue sections) appear: a dark zone containing cycling cells (centroblasts) and a light zone where B cells are smaller and less densely packed (centrocytes) [68]. While dividing, centroblasts introduce mutations into the V-region-encoding gene segments, a process known as somatic hypermutation (SHM) that lead to affinity maturation.…”