Intrinsic Constraint on Plasmablast Growth and Extrinsic Limits of Plasma Cell Survival

Abstract

B cells recruited into splenic antibody responses grow exponentially, either in extrafollicular foci as plasmablasts, or in follicles where they form germinal centers. Both responses yield plasma cells. Although many splenic plasma cells survive <3 d, some live much longer. This study shows that early plasma cell death relates to a finite capacity of the spleen to sustain plasma cells rather than a life span endowed by the cell's origin or the quality of antibody it produces. Antibody responses were compared where the peak numbers of plasma cells in spleen sections varied between 100 and 5,000 cells/mm2. In each response, plasmablast clones divided some five times, with the peak numbers of plasma cells produced relating directly to the number of B cells recruited into the response. The spleen seems to have the capacity to sustain between 20 and 100 plasma cells/mm2. When this number is exceeded, there is a loss of excess cells. Immunoglobulin variable region gene sequencing, and 5-bromo-2′-deoxyuridine pulse–chase studies indicate that long-lived splenic plasma cells are a mixture of cells derived from the extrafollicular and germinal center responses and cells derived from virgin and memory B cells. Only a proportion has switched immunoglobulin class.

Analysis of Marginal Zone B Cell Development in the Mouse with Limited B Cell Diversity: Role of the Antigen Receptor Signals in the Recruitment of B Cells to the Marginal Zone

“…The robust activation of B cells has been reported to occur by immunizing QM mice with a T cellindependent (TI)-Ag NP-Ficoll, indicating that the MZ B cells of QM mice can participate in TI Ag response (46). The MZ B cells bearing M167-or VH81X-autoreactive BCR have been previously shown to respond to TI Ags in vitro and in vivo (8,13).…”

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

“…Hence, the recruitment of PCs to BM niches and their local survival represent independently governed processes. They seem intertwined, however, in that the recruitment process assures appropriate contacts of the cellular players, which need to dock together for long-term Ab production by BMPCs (2,8). In this concept, additional players such as dendritic cells shown to support PC function (29) could also be recruited in this functional BMPC niche.…”

A Division-Linked Mechanism for the Rapid Generation of Ig-Secreting Cells from Human Memory B Cells

“…Nevertheless, if the changing sensitivity of activated memory B cells to CD40L observed in vitro can be extrapolated to the in vivo situation, it is possible that CD38 Ϫ and CD38 ϩ ISCs represent short-lived and long-lived ISCs, respectively (14, 50 -53). Thus, acquisition of CD38 expression may correlate with selection into a population of T cell stimulation-independent, rapidly proliferating plasma cell precursors, which contribute to an initial expansion of the selected population of ISCs (9,10,47,49,54). The rapidly dividing CD38 ϩ ISCs presumably then acquire altered homing characteristics, resulting in their migration to sites including bone marrow (55,56), where they undergo terminal differentiation to yield long-lived quiescent CD38 ϩ plasma cells (38,45,52,53,57,58).…”