Antigen-capturing cells can masquerade as memory B cells.
As well as classically defined switched immunoglobulin isotype-expressing B cells, memory B cells are now thought to include IgM-expressing cells and memory cells that lack B cell lineage markers, such as B220 or CD19. We set out to compare the relative importance of memory B cell subsets with an established flow cytometry method to identify antigen-specific cells. After immunization with PE, we could detect B220+ and, as reported previously, B220- antigen-binding cells (McHeyzer-Williams, L.J., M. Cool, and M.G. McHeyzer-Williams. 2001. J. Immunol. 167:1393-1405). The B220-PE+ cells bore few markers typical of B cells, but resembled myeloid cells. Further analysis of the antigen-binding characteristics of these cells showed that, upon immunization with two fluorescent proteins, the B220- cells could bind both. Furthermore, this subpopulation was detected in RAG1-/- mice after transfer of anti-PE mouse serum. These data strongly suggest that these cells capture serum Ig, via Fc receptors, and thus appear antigen-specific. Investigation of these antigen-capturing cells in a variety of knockout mice indicates that they bind monomeric IgG in an FcgammaR1 (CD64)-dependent manner. We find no evidence of a B220- memory B cell population that is not explicable by antigen-capturing cells, and warn that care must be taken when using antigen-specificity or surface IgG as an indicator of B cell memory.
Bell
Jennifer
J
Institute of Cell, Animal, and Population Biology, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Rd, Edinburgh EH9 3JT UK.
Gray
David
D
D000818:Animals; D000941:Antigens / Q000276:immunology*; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D018398:Homeodomain Proteins / Q000502:physiology; D007074:Immunoglobulin G / Q000145:classification / Q000502:physiology; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010799:Phycoerythrin / Q000032:analysis / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology; D012542:Scattering, Radiation
D000941:Antigens; D018941:Antigens, CD19; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D017452:Receptors, IgG; D010799:Phycoerythrin; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens