Noncognate contact-dependent B cell activation can promote IL-4-dependent in vitro human IgE synthesis.
We have previously shown that IL-4 is an essential mediator for the synthesis of human IgE in vitro. In this study we demonstrate that prior physical contact with T cells is required by B cells to synthesize IgE in response to IL-4. Both autologous and allogeneic freshly prepared T cells were consistently able to support IL-4-dependent IgE synthesis, provided that they were added to B cells together with, or before, the addition of IL-4. In addition, most CD4+, as well as a proportion of CD8+, PHA-induced T cell clones (TCC) established from two HLA-DR incompatible donors, supported, in the presence of exogenous IL-4, the synthesis of IgE in B cells from the majority of individuals tested including both donors of cloned T cells. An alloreactive TCC able to produce IL-4 in response to HLA-DR4+ B cells and to induce HLA-DR4+ B cells to synthesize IgE, acquired the ability to support IgE synthesis by B cells lacking the appropriate alloantigen provided that exogenous IL-4 was added. Although the ability of freshly prepared T cells to support IgE synthesis was consistently abrogated by fixation with paraformaldehyde (PF), such a treatment variably affected the IgE-inducing ability of TCC. Preactivation with anti-CD3 before treatment with PF maintained or even enhanced the ability of TCC to support IL-4-dependent IgE synthesis. More importantly, preactivation with anti-CD3, followed by fixation with PF, enabled TCC, apparently devoid of IgE-inducing activity in unfixed condition, to support IL-4-dependent IgE synthesis. Taken together these data suggest that at least two signals are involved in the triggering of human B cells to IgE production: the first is delivered by a T-B cell contact and the second by IL-4. The physical signal delivered by T cells does not necessarily consist of cognate interaction. Non-cognate contact-dependent induction of B cells to IgE synthesis in response to IL-4 appears to be related to molecule(s) distinct from the TCR/CD3 complex, but fully expressed on the membrane of TCR/CD3-activated T cells.
Parronchi
P
P
Division of Allergology and Clinical Immunology, University of Florence, Italy.
Tiri
A
A
Macchia
D
D
De Carli
M
M
Biswas
P
P
Simonelli
C
C
Maggi
E
E
Del Prete
G
G
Ricci
M
M
Romagnani
S
S
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D017252:CD3 Complex; D005557:Formaldehyde / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D011108:Polymers / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000949:Histocompatibility Antigens Class II; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; D005557:Formaldehyde; D015847:Interleukin-4; D007073:Immunoglobulin E; C003043:paraform