Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen[1] – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes (through somatic hypermutation aimed at achieving higher affinity) during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages.

The initiation of germinal center formation involves the interaction between B and T cells in the interfollicular area of the lymph node, CD40-CD40L ligation, NF-kB signaling and expression of IRF4 and BCL6.

[3][4][5][6] As they undergo rapid and mutative cellular division, B cells of the germinal center's dark zone are known as centroblasts.

Specifically, the expression of IRF4 and BCL6 transcription factors are both required for germinal center development and regulated by NF-kB signaling.

[3][5] Somatic hypermutation, a process in which the activation-induced cytidine deaminase (AID) enzyme randomly mutates the variable regions of the antibody and alters their affinity for the antigen, occurs in the dark zone.

[4] B cells expressing antibodies that have decreased affinity for the antigen following somatic hypermutation undergo apoptosis, while B cells expressing antibodies that have increased affinity for the antigen after somatic hypermutation migrate to the light zone for further selection.

[3] Finally, the positively-selected GC B cells (cMyc+) are "licensed," which means they are ready to be sent back to the dark zone of the germinal center where they will further proliferate and be mutated by somatic hypermutation.

[5] T follicular helper cells mediate the germinal center reaction in two key ways.

This interaction upregulates the NF-kB signaling pathway, which stimulates the division of GC B cells.

The upregulation of the NF-kB signaling pathway results in greater expression of IRF4, a transcription factor that is essential for plasma cell differentiation.

[6] The progression of the germinal center response results in plasma cells that secrete higher affinity antibodies having an increased lifespan and being sent to the bone marrow.

[6] The morphology of GCs is very specific and shows properties which are characteristic for different stages of the reaction.

Under evolutionary new conditions, when elevated body temperature contributed to the increased rates of microorganism proliferation, dissemination in tissues, and their antigenic diversification[9] , these temporary but constantly observed histological structures turned to be beneficial as their unique microenvironment could provide the conditions favourable for the shift from the initial broad to subsequent specific immune response resulting in B lineage cells differentiated to those producing high-affinity Ab and maintaining long-lasting humoral immune memory.

[10] Among cold-blooded vertebrates, fish seem have functionally analogous structures represented by "clusters of Aicda+ cells encircled by pigmented 'melano-macrophages'".