Evidence That Marginal Zone B Cells Possess an Enhanced Secretory Apparatus and Exhibit Superior Secretory Activity

Abstract

Marginal zone B (MZB) cells are the first splenic B cells to initiate Ab secretion against polysaccharide-encapsulated Ags in vivo. This swift MZB cell response can be reproduced in vitro as LPS treatment induces Ab secretion in as little as 12 h. Conversely, in vitro LPS treatment of splenic follicular B (FOB) cells results in Ab secretion after 2–3 days. The basis for these distinct response kinetics is not understood. We performed ex vivo analysis of resting and LPS-stimulated murine MZB and FOB cells and found that MZB cells express higher levels of the LPS TLR complex RP105/MD-1 and respond to much lower concentrations of LPS than do FOB cells. Furthermore, increasing doses of LPS do not accelerate the kinetics by which FOB cells transition into Ab secretion. Ultrastructural analysis of resting cells demonstrated that rough endoplasmic reticulum is more abundant in MZB cells than in FOB cells. Additionally, RT-PCR and immunoblot analyses revealed that numerous endoplasmic reticulum resident chaperones and folding enzymes are expressed at greater levels in resting MZB cells than in resting FOB cells. Although both LPS-stimulated MZB and FOB cells increase expression of these factors, MZB cells exhibit a more rapid increase that correlates with accelerated kinetics of Ab secretion and higher per cell output of secreted IgM. These data indicate that MZB cells are equipped for exquisite sensitivity to bacterial components like LPS and poised for rapid, robust Ab production, making MZB cells ideally suited as frontline defenders in humoral immunity.

Different Kinetics of Blimp-1 Induction in B Cell Subsets Revealed by Reporter Gene

“…The quantitative RT-PCR for this gene indicated that in MZ and B1 cells, which are able to rapidly become ASCs, the level of xbp-1 is not elevated. This supports recently published results for MZ and B2 cells (6) showing that transcripts encoding several ER resident proteins important for protein folding and secretion were elevated in resting MZ B cells compared with resting splenic B2 B cells despite similarities in xbp-1 expression. These results, in combination with the other results described from these quantitative RT-PCRs, indicate that B1 cells show a transcriptional priming that predisposes these cells toward a rapid response to simulation.…”

TLR Agonists Selectively Promote Terminal Plasma Cell Differentiation of B Cell Subsets Specialized in Thymus-Independent Responses

“…This may be due, in part, to the fact that they possess an enhanced secretory apparatus (21). This could also be linked to the constitutively high levels of Blimp-1 and low level of Bcl-6 they express as compared with FO B cells.…”

Genetic Immunization Converts theTrypanosoma cruziB-Cell Mitogen Proline Racemase to an Effective Immunogen

“…The different contributions of these two B-cell populations to immunity during infectious disease are still under investigation (3,29,39,42,60). While differences in MZ and FM cell responsiveness to lipopolysaccharide (LPS) and other Toll-like receptor (TLR) ligands have been reported (21,30), the responses of these B-cell subsets to pathogen-derived B-cell mitogenic proteins have remained largely unexplored. Due to their different locations and functions, these two B-cell subsets may play different roles during pathogen-induced polyclonal B-cell activation.…”