Extrafollicular and other non-germinal center B cell responses.

B cells exist as different subsets shaped by developmental cues, the activation environment, and the magnitude and nature of immune stimulus; such heterogeneity is essential for tailored immune responses. From both mouse and human studies, the past decade has seen significant advances in our understanding of the wide variety of B cell activation pathways. However, the terms currently used to specify the type of B cell response have not kept up with this progress. Furthermore, a myopic focus on the germinal center (GC) response for the generation of protective or pathogenic antibodies has left other types of T cell-dependent but GC-independent antibody responses loosely categorized together as "extrafollicular (EF) responses" resulting in ambiguity with respect to cellular and molecular mechanisms. Based on the historical definition, an EF B cell response refers to an activation/differentiation path that is anatomically distinct from the GC and occurs outside of the B cell follicle. If anatomical location helps dictate functional outcomes, it is time to reconsider broad use of the term EF. Nomenclature is always imperfect, but a rethinking of current B cell nomenclature is warranted. Doing so could lead to a clearer understanding of different cellular pathways to humoral immunity and help reveal unanswered questions in B cell biology.