title: Functional activity of natural antibody is altered in Cr2-deficient mice.
abstract: The major source of natural IgM Abs are B-1 cells, which differ from conventional B cells in their anatomic location, cell surface phenotype, restricted usage of particular V(H) genes and limited use of N-region addition during V-D-J rearrangement. The origin of B-1 cells is unclear. However, they are capable of self-renewal and their development is sensitive to signaling via the B cell receptor, as genetic defects that impair the strength of the signal often result in limited development. These findings suggest that B-1 cells require either an intrinsic signal, or contact with Ag, for positive selection and expansion and/or maintenance in the periphery. In support of interaction with cognate Ag, deficiency in the complement receptors CD21/CD35 results in a 30-40% decrease in the CD5(+) B-1 population. To determine whether this reduction reflects a loss of certain specificities or simply a proportional decline in the repertoire, we examined peritoneal B cells isolated from Cr2(+) and Cr2(def) mice for recognition of a B-1 cell Ag, i.e., phosphatidylcholine, and assayed for injury in an IgM natural Ab-dependent model of reperfusion injury. We found a similar frequency of phosphatidylcholine-specific CD5(+) B-1 cells in the two strains of mice. By contrast, the Cr2(def) mice have reduced injury in the IgM-dependent model of reperfusion injury. Reconstitution of the deficient mice with pooled IgM or adoptive transfer of Cr2(+) peritoneal B cells restored injury. These results suggest that complement receptors CD21/CD35 are important in maintenance of the B-1 cell repertoire to some, but not all, specificities.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Reid
authors.forename: Sean
authors.initials: S
authors.lastname: Woodcock
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Hechtman
authors.forename: Francis D
authors.initials: FD
authors.lastname: Moore
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018956:CD5 Antigens / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D007275:Injections, Intravenous; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000166:cytology; D010713:Phosphatidylcholines / Q000276:immunology; D017464:Receptors, Complement 3d / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000517:prevention & control
chemical_list: D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D007075:Immunoglobulin M; D010713:Phosphatidylcholines; C499308:Rag2 protein, mouse; D017464:Receptors, Complement 3d; C064655:V(D)J recombination activating protein 2