B cell-B cell interaction through intercellular adhesion molecule-1 and lymphocyte functional antigen-1 regulates immunoglobulin E synthesis by B cells stimulated with interleukin-4 and anti-CD40 antibody.
IgE synthesis by purified human B cells is induced by two signals: a class switching factor, most commonly interleukin (IL)-4, and the engagement of CD40, which is activated through its interaction with CD40 ligand (CD40L) expressed on activated T cells. Thus, the combination of IL-4 and anti-CD40 monoclonal antibody (mAb) has been shown to stimulate IgE production in vitro by highly purified B cells. In this T cell-independent system, strong homotypic aggregation of B cells is observed prior to the production of IgE. Flow cytometric analysis and cell binding assays showed that the stimulation of purified B cells with anti-CD40 mAb plus IL-4 resulted in a striking increase of intercellular adhesion molecule (ICAM)-1(CD54) expression, an induction of CD43 and an avidity change of lymphocyte functional antigen (LFA)-1(CD11a/CD18), with little augmentation of CD18 expression. Addition of anti-ICAM-1 mAb caused an inhibition of homotypic aggregation but augmented IgE synthesis by B cells stimulated with anti-CD40 mAb and IL-4, although it did not affect B cell proliferation or IL-6 production by the B cells. Among the mAb against counter-receptors for ICAM-1 tested, anti-CD11a mAb suppressed IgE synthesis, while anti-CD18 mAb and anti-CD43 mAb had little effect. The enhancing or inhibitory effect of anti-ICAM-1 mAb or anti-CD11a mAb on IgE production was achieved by the increased or decreased expression of germline C epsilon transcripts by B cells stimulated with anti-CD40 mAb and IL-4. These results indicate that B cell-B cell interaction through ICAM-1 and one of its counter receptors, LFA-1, regulates IgE synthesis by modulating C epsilon germ-line transcription.
Katada
Y
Y
Department of Medicine III, Osaka University Medical School, Japan.
Tanaka
T
T
Ochi
H
H
Aitani
M
M
Yokota
A
A
Kikutani
H
H
Suemura
M
M
Kishimoto
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism*; D018821:CD18 Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D004357:Drug Synergism; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D012795:Sialoglycoproteins / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D019013:CD40 Antigens; D007127:Immunoglobulin Constant Regions; D051917:Leukosialin; D016169:Lymphocyte Function-Associated Antigen-1; C465014:SPN protein, human; D012795:Sialoglycoproteins; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007073:Immunoglobulin E