Figure 2.

Elimination of autoreactive B cells by peripheral tolerance mechanisms at various checkpoints. (A) Maturation of transitional B cells takes place in the spleen. Transitional B cells that strongly bind self-antigens present in the spleen undergo clonal deletion or anergy, which reduces the frequency of autoreactive B cells. The transitional B cells that moderately bind self-antigens mature into naive B cells. Naive B cells predominantly encounter antigens within lymph nodes and the spleen. Activation of naive B cells is dependent on the binding of antigens and interaction with CD4⁺ T helper (T_H) cells with the same antigen specificity in which B cells receive costimulatory signals. Naive B cells that do not have interaction with T_H cells undergo clonal deletion or anergy, which further reduces the frequency of autoreactive B cells. (B) Activated B cells enter germinal centers within lymph nodes and the spleen, undergo somatic hypermution (SHM) and isotype switching, and ultimately mature into memory B cells and long-lived plasma cells. These maturation processes are dependent on costimulatory signals from CD4⁺ follicular T helper (T_FH) cells with the same antigen specificity. Clonal deletion is induced in B cells that do not receive costimulatory signals from T_FH cells, resulting in the removal of autoreactive B cells from the B cell pool. Figure was created with BioRender.