Stimulation of human IgE production by a subset of anti-CD21 monoclonal antibodies: requirement of a co-signal to modulate epsilon transcripts.
CD21, the receptor for Epstein-Barr virus (EBV) and the complement receptor-2 (CR2), was recently found to interact specifically with CD23, a low-affinity receptor for IgE, and to regulate IgE production. Therefore, the effect of different anti-CD21 monoclonal antibodies (mAb) on IgE synthesis by blood mononuclear cells was investigated. One anti-CD21 mAb, BU-33, was able to increase significantly (more than threefold) interleukin-4 (IL-4)-induced IgE synthesis, whereas HB-5, OKB-7 and B2 anti-CD21 mAb had no effect. BU-33 had no effect on IgG and IgA production and produced only a moderate increase in IgM production. Recombinant, 29,000 MW, soluble CD23 (sCD23) expressed in COS cells exhibited the same IgE-enhancing activity. BU-33 was the best inhibitor of CD23-liposome binding to the CD21-positive cell line RPMI-8226 when compared to the other anti-CD21 mAb tested. BU-33 identified a different epitope on CD21. The effect of BU-33 on IgE production by purified tonsillar B cells and highly purified germinal centre B cells, was dependent on the presence of T cells or anti-CD40 mAb stimulation. Molecular analysis revealed that BU-33 alone failed to induce germline epsilon mRNA but increased the IL-4-induced germline epsilon transcription levels. Moreover, BU-33 had a synergistic effect on anti-CD40 mAb or T-cell-induced productive epsilon transcript expression. These results therefore indicate that the CD23-CD21 interaction needs a co-signal for B-cell differentiation towards IgE production.
Henchoz
S
S
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Gauchat
J F
JF
Aubry
J P
JP
Graber
P
P
Pochon
S
S
Bonnefoy
J Y
JY
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E