Figure 2.  Follicular and extrafollicular origins of
autoantibody-producing plasma cells. Autoreactive red pulp B
cells and follicular (FO) B cells that encounter autoantigens in
conjunction with Toll-like receptor and other innate signals
differentiate to autoantibody (autoAb)-producing antibody-
forming cells in extrafollicular bridging channels, where
marginal zone (MZ) dendritic cells (DCs) may promote autoAb
responses and plasma cell (PC) survival through direct antigen
presentation and production of soluble mediators such as IL-6,
BAFF, or APRIL. Extrafollicular autoAb responses involve
activation-induced deaminase-dependent class-switch
recombination and somatic hypermutation (SHM) that in some cases
is also T-cell independent. FO B cells may additionally migrate
to germinal centers (GCs) within follicles where autoreactive B
cells arising through SHM may escape selection mechanisms via
B-cell intrinsic or extrinsic factors to become additional
sources of pathogenic autoAbs in genetically predisposed an