Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones.
In the present study, it is demonstrated that cloned surface IgM-positive human B cells can be induced to proliferate and to switch with high frequencies to IgG4 and IgE production after a contact-mediated signal provided by T cell clones and interleukin 4 (IL-4). This T cell signal is antigen nonspecific and is provided by activated CD4+ cells, whereas activated CD8+ or resting CD4+ T cell clones are ineffective. 15-35% of the B cell clones cultured with cloned CD4+ T cells and IL-4 produced antibodies; 35-45% of those wells in which antibodies were produced contained IgE and IgG4. In addition to B cell clones that produced IgG4 or IgE only, B cell clones producing multiple isotypes were observed. Simultaneous production of IgG4 and IgE, IgM, IgE, and IgM, or IgG4 and IgE was detected, suggesting that during clonal expansion switching might occur in successive steps from IgM to IgG4 and IgE. In addition, production of only IgM, IgG4, and IgE during clonal expansion indicates that this isotype switching is directed by the way a B cell is stimulated and that it is not a stochastic process.
Gascan
H
H
Human Immunology Department, DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, California 94304.
Gauchat
J F
JF
Roncarolo
M G
MG
Yssel
H
H
Spits
H
H
de Vries
J E
JE
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D002999:Clone Cells; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E