Peritoneal Cavity B Cells Are Precursors of Splenic IgM Natural Antibody-Producing Cells

Abstract

Peritoneal cavity B-1 cells are believed to produce IgM natural Abs. We have used α1,3-galactosyltransferase-deficient (GalT−/−) mice, which, like humans, produce IgM natural Abs against the carbohydrate epitope Galα1,3Gal (Gal), to demonstrate that peritoneal cavity B-1b cells with anti-Gal receptors produce anti-Gal IgM Abs only after LPS stimulation. Likewise, peritoneal cavity cells of GalT−/− and wild-type mice do not produce IgM Abs of other specificities without LPS stimulation. Development of Ab-secreting capacity is associated with loss of CD11b/CD18 (Mac-1) expression. In contrast, there are large numbers of cells producing anti-Gal and other IgM Abs in fresh splenocyte preparations from GalT−/− and (for non-Gal specificities) wild-type mice. These cells are Mac-1− but otherwise B-1b-like in their phenotype. We therefore hypothesized a pathway wherein peritoneal cavity B cells migrate into the spleen after activation in vivo and lose Mac-1 expression to become IgM Ab-producing cells. Consistent with this possibility, splenectomy reduced anti-Gal Ab production after immunization of GalT−/− mice with Gal-positive rabbit RBC. Furthermore, splenectomized B6 GalT−/−, Ig μ-chain mutant (μ−/−) (both Gal- and B cell-deficient) mice produced less anti-Gal IgM than nonsplenectomized controls after adoptive transfer of peritoneal cavity cells from B6 GalT−/− mice. When sorted GalT−/− Mac-1+ peritoneal cavity B cells were adoptively transferred to B6 GalT−/−, μ−/− mice, IgM Abs including anti-Gal appeared, and IgM-producing and Mac1− B cells were present in the spleen 5 wk after transfer. These findings demonstrate that peritoneal cavity Mac-1+ B-1 cells are precursors of Mac-1− splenic IgM Ab-secreting cells.

Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions

“…5A). The facts that PC1 lo cells migrate more readily to the spleen than PC1 hi cells and that peritoneal B-1 cells become secretory only after migration to the spleen (20) suggested that PC1…”

“…These antibodies are encoded by "stereotyped" germ-line sequences and can be of IgM, IgG, or IgA classes. The lymphoid compartments in which B-1a cells secrete natural antibodies have been shown to include the spleen and BM (20)(21)(22). Recently, Cole et al showed that spleens of mice immunized with the atypical LPS of Francisella tularensis contain antigen-specific plasma cells of B-1a origin (23).…”

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

“…6 Left). Discussion B-1a cells are very important players in both innate and adaptive immunity (1,(14)(15)(16)(17)(18)(19). In mice that have not been intentionally immunized or infected, they produce much of the ''natural'' serum IgM and, in mice stimulated with LPS or other microbial products, they produce much of the polyclonal antibody response (2,3,20).…”

Infection-Induced Marginal Zone B Cell Production of Borrelia hermsii-Specific Antibody Is Impaired in the Absence of CD1d

“…Like B1b cells, these cells bridge the innate and adaptive immune systems, because they have the capacity to respond to specific foreign Ag more rapidly than conventional T and B lymphocytes (10). MZB cells can be distinguished from follicular B cells by their complement receptor 2 (CD21) high CD1d high CD23 low phenotype (11,12) and from splenic B1 B cells by their CD21 high CD43 low expression (13). Based on studies using inert particles and heat-killed bacteria, it has been postulated that reduced CD23 expression, a negative regulator of B cells, may allow MZB cells to produce a more rapid Ab response compared with follicular B cells, and that CD21 high expression facilitates MZB cell interaction with complementcoated blood-borne Ag (14).…”