CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses

J Immunol. 2005 Sep 1;175(5):2859-67. doi: 10.4049/jimmunol.175.5.2859.


The adaptive immune response is tightly regulated to limit responding cells in an Ag-specific manner. On B cells, coreceptors CD21/CD19 modulate the strength of BCR signals, potentially influencing cell fate. The importance of the CD95 pathway was examined in response of B cells to moderate affinity Ag using an adoptive transfer model of lysozyme-specific Ig transgenic (HEL immunoglobulin transgene (MD4) strain) B cells. Although adoptively transferred Cr2+/+ MD4 B cells are activated and persist within splenic follicles of duck egg lysozyme-immunized mice, Cr2-/- MD4 B cells do not. In contrast, Cr2-/- MD4 lpr B cells persist after transfer, suggesting that lack of CD21/CD35 signaling results in CD95-mediated elimination. Cr2 deficiency did not affect CD95 levels, but cellular FLIP (c-FLIP) protein and mRNA levels were reduced 2-fold compared with levels in Cr2+/+ MD4 B cells. In vitro culture with Cr2+/+ MD4 B cells demonstrated that equimolar amounts of rHEL-C3d3 were more effective than hen egg lysozyme alone in up-regulating c-FLIP levels and for protection against CD95-mediated apoptosis. Collectively, this study implies a mechanism for regulating B cell survival in vivo whereby the strength of BCR signaling (including coreceptor) determines c-FLIP levels and protection from CD95-induced death.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD19 / physiology*
  • Apoptosis
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Cell Survival
  • Complement C3d / immunology
  • Intracellular Signaling Peptides and Proteins / analysis
  • Mice
  • Mice, Inbred C57BL
  • Muramidase / immunology
  • Receptors, Complement 3b / physiology
  • Receptors, Complement 3d / physiology*
  • Signal Transduction / physiology*
  • fas Receptor / physiology


  • Antigens, CD19
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Cflar protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • fas Receptor
  • Complement C3d
  • Muramidase