Division and differentiation of natural antibody-producing cells in mouse spleen

Abstract

B-1a cells reside in both the peritoneal cavity and the spleen. LPS stimulates splenic B-1a to differentiate to plasma cells producing natural IgM specific for microbial and self antigens. However, there are conflicting views as to whether the B-1a cells divide before this differentiation occurs, and hence how the resident B-1a population is maintained in the spleen. Studies here resolve this dispute in favor of both sides: we show that (some or all) B-1a cells resident in the spleen respond to LPS by differentiating to plasma cells immediately, without dividing; however, we also show that additional B-1a cells immigrate into the spleen after LPS stimulation and divide at least once before differentiating. Importantly, the studies we presently describe reveal the complex cell migration and differentiation events that collectively underlie the rapid production of natural antibodies in response to in vivo LPS stimulation. Thus, the studies present a different view of the roles that B-1a cells play in the early phases of the innate immune response.B-1 ͉ CD138 ͉ CD5 ͉ lipopolysaccharide ͉ plasma cells

Antigen-specific B-1a antibodies induced byFrancisella tularensisLPS provide long-term protection againstF. tularensisLVS challenge

“…S3) stimulated by Ft-LPS immunization incorporate BrdU, indicating that these cells divide at least once during, before, or after differentiating to CD138 ϩ intracellular IgM ϩ plasma cells. This extensive cell division, contrasts markedly with responses to Typhi-LPS, where a sizable proportion of responding splenic B-1a cells differentiate to plasma cells within 24 h without dividing (20).…”

Necroptosis suppresses inflammation via termination of TNF- or LPS-induced cytokine and chemokine production

“…Error bars represent the mean ± S.E.M. of triplicate cell cultures hours: 33,34 As shown in Figure 7a, LPS administration led to a dramatic reduction in peritoneal cellularity, which was significantly inhibited in LPS/zVAD-treated animals. However, it should also be noted that zVAD alone also led to a reduction in peritoneal cellularity.…”

“…Previous studies have shown that LPS induces cell death in the peritoneal cavity, as well as activation and efflux of resident macrophages and lymphocytes. 32,33 The latter events are mirrored by an increase in splenic cellularity, composed of migrating Figure 3 Caspase activity is not required for TNF-induced cytokine production. (a) HeLa cells were pretreated for 1 h with the indicated concentrations of zVAD, followed by addition of TNF-related apoptosis-inducing ligand (TRAIL; 100 ng/ml).…”

Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells

“…The maintenance of B1 cells encompasses a dynamic set of processes involving relocalization of PEC B1 cells upon antigen sensing to the effector sites (spleen or gut), proliferation and secretion of antibodies, and the return to the PEC of cells that failed to differentiate into plasma cells (12,19,21).…”