B-1 cells in the bone marrow are a significant source of natural IgM.
Natural IgM antibodies secreted in the absence of antigenic challenge are important contributors to antimicrobial immunity and tissue homeostasis. Early studies identified BM and, to a lesser extent the spleen, as main tissue sources of this spontaneously secreted IgM. However, the responsible B-cell subset has never been identified. Using multicolor flow cytometry, cell sorting and chimeric mice in which B-1 and B-2 cells and their secreted antibodies are distinguished by their Ig-allotype, we unequivocally identify the natural IgM-secreting cells in spleen and, for the first time, in the BM as IgM(+)  IgD(lo/-) CD19(hi)  CD43(+)  CD5(+/-)  B-1 cells. The newly identified population of BM B-1 cells shows many of the phenotypic characteristics of splenic B-1 cells but is distinct from B-1 cells in the peritoneal cavity, which generate at best very small amounts of IgM. Antibody-secreting spleen and BM B-1 cells are distinct also from terminally differentiated plasma cells generated from antigen-induced conventional B cells, as they express high levels of surface IgM and CD19 and lack expression of CD138. Overall, these data identify populations of non-terminally differentiated B-1 cells in spleen and BM as the most significant producers of natural IgM.
The Graduate Group in Immunology, University of California, Davis, Davis, CA 95616, USA.
Youn Soo
YS
Choi
Jacquelyn A
JA
Dieter
Kristina
K
Rothaeusler
Zheng
Z
Luo
Nicole
N
Baumgarth
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053668:Syndecan-1; D018183:Transplantation Chimera
D018941:Antigens, CD19; D007126:Immunoglobulin Allotypes; D007075:Immunoglobulin M; D053668:Syndecan-1; C033027:secretory IgM