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: Russell R Reid, Sean Woodcock, Alexander Shimabukuro-Vornhagen, William G Austen Jr, Lester Kobzik, Ming Zhang, Herbert B Hechtman, Francis D Moore Jr, Michael C Carroll
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 10 Pg. 5433-40 (Nov 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12421918 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD5 Antigens
• DNA-Binding Proteins
• Immunoglobulin M
• Phosphatidylcholines
• Rag2 protein, mouse
• Receptors, Complement 3d
• V(D)J recombination activating protein 2

Topics

• Adoptive Transfer
• Animals
• Antibody Specificity (genetics)
• B-Lymphocyte Subsets (immunology, metabolism, transplantation)
• CD5 Antigens (biosynthesis)
• DNA-Binding Proteins (deficiency, genetics)
• Female
• Immunity, Innate (genetics)
• Immunoglobulin M (administration & dosage, blood, isolation & purification, physiology)
• Injections, Intravenous
• Lymphocyte Count
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Peritoneum (cytology)
• Phosphatidylcholines (immunology)
• Receptors, Complement 3d (biosynthesis, deficiency, genetics)
• Reperfusion Injury (genetics, immunology, prevention & control)