Functional activity of natural antibody is altered in Cr2-deficient mice

J Immunol. 2002 Nov 15;169(10):5433-40. doi: 10.4049/jimmunol.169.10.5433.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


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