Peritoneal cavity B cells are precursors of splenic IgM natural antibody-producing cells.
Peritoneal cavity B-1 cells are believed to produce IgM natural Abs. We have used alpha1,3-galactosyltransferase-deficient (GalT(-/-)) mice, which, like humans, produce IgM natural Abs against the carbohydrate epitope Galalpha1,3Gal (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 micro -chain mutant ( micro (-/-)) (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(-/-), micro (-/-) 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.
Kawahara
Toshiyasu
T
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Ohdan
Hideki
H
Zhao
Guiling
G
Yang
Yong-Guang
YG
Sykes
Megan
M
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000921:Antibody-Producing Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D017710:Lymphocyte Transfusion; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000166:cytology*; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*
D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D016177:Macrophage-1 Antigen; D005700:Galactosyltransferases