3.3.3. Formation of Germinal-Like Structures

Germinal centres (GCs) were described for the first time by Walther Flemming in 1884 [140]. GCs are specific region in secondary lymphoid tissues such lymph nodes and spleen. GCs provide the environment for proliferation of mature B cells, differentiation and mutation of their immunoglobulin variable-region gene segments during a process called somatic hypermutation, which generates a diversity of clones. Following this process, the cells migrate from the dark zone to the lighter zone of the lymphoid tissues, where the affinity of immunoglobulins is tested on follicular dendritic cells (FDC) and follicular helper T cells (TFH) cells presenting the antigens. The non-selected cells undergo apoptosis while the selected cells are stimulated by T cells to undergo class switch recombination and differentiation into antibody-producing plasma cells or memory B cells [141,142]. SG from SS patients can contain similar GC structures made of T, B, and plasma cells, macrophages, and follicular dendritic cells [143]. Given the strong similarity of SG GC with the lymphoid organ GC, the SG GC observed in SS patients were defined as ectopic GC-like structures, also known as "tertiary lymphoid organs" [144]. Several studies have reported the association between GCs and the immunopathological features of SS [145]. Other important studies have observed a 6.5- to 15.6-fold increased risk to develop non-Hodgkin lymphomas in SS with an elevated presence of GCs [146,147].
