What is and what should always have been: long-lived plasma cells induced by T cell-independent antigens

Abstract

It is well accepted that Ag-induced B cell differentiation often results in the generation of exceptionally long-lived plasma cells. Much of the work supporting this viewpoint stems from studies focused on germinal center-derived plasma cells secreting high-affinity isotype-switched Abs in mice immunized with T cell-dependent Ags. In contrast, less attention has been devoted to understanding Ab responses to T cell-independent Ags and pathogens. In this study, we review recent work showing that T cell-independent Ags consisting of either polysaccharides or LPSs also induce the formation of long-lived plasma cells, despite their general inability to sustain germinal center responses. This new information provides a framework for more fully understanding the forces underlying immunity to pathogens that resist T cell recognition and the extracellular cues governing plasma cell longevity.

Figure 1. Contrasting models for origins of long-lived plasma cells

(A) Standard model indicating that bone marrow plasma cells derive chiefly, if not exclusively, from GCs. (B) Alternative model illustrating that bone marrow plasma cells also derive from early extrafollicular plasma cell pools. Whereas GCs may serve as the chief source of bone marrow plasma cells (multiple arrows), dotted lines denote current uncertainty about the relative contribution of memory B cells and extrafollicular antibody secreting cells to long-lived plasma cell pools.