Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.

Abstract

The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutations of the CD40L gene were reported responsible for defective class switching of B cells in an X-linked immunodeficiency with hyper IgM (X-HIM).We studied four affected males from three families and found three independent mutations including new mutations of CD40L gene. In every X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce class switching from IgM to IgG or IgA, even in the presence of Staphylococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD40L on their surface, also did not rescue IgG or IgA induction by X-HIM peripheral blood B cells in vitro. But signaling through CD40 induced both B cell proliferation and IgE secretion when IL-4 was added to the culture.Taken together, these results show that in vitro signaling through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD4OL interaction might be necessary for IgG and IgA differentiation in X-HIM. (J. Clin. Invest. 1995. 95:510-514.)

Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.

“…On the other hand, it is reported that apparent IgG and IgA production is not observed with anti-CD40 plus IL-10 (32). In our cases, B cells from some but not all of our XHIM patients did not secrete IgG in response to anti-CD40 plus IL-10 or SAC plus IL-2, which is similar to the reported findings of several XHIM patients (32,40). However, in disagreement with the XHIM patients reported (35), IgA secretion was absent in all our patients regardless of the B cell stimulation systems (Table II).…”

“…Adequate IgE secretion was not detected in the other three patients. However, it is interesting to note that, in accordance with the results by Saiki et al (32), the addition of IL-10 to anti-CD40 plus IL-4 resulted in measurable levels of IgE synthesis in Patient IN (Table IV) …”

“…In disagreement with the data, Saiki et al (32) reported that there was no induction of IgG and IgA secretion in four XHIM patients. In four of our patients (Patient IN, TY, AY, and RM), marginal levels of IgG secretion, but no IgA, were observed after the stimulation.…”

“…Several reports indicate that the patient B cells have ability to produce IgG, IgA, or IgE in the presence of anti-CD40 plus cytokines (3,31,32,36,39). On the other hand, it is reported that apparent IgG and IgA production is not observed with anti-CD40 plus IL-10 (32).…”

The different process of class switching and somatic hypermutation; a novel analysis by CD27− naive B cells

“…Differentiation of CD27 Ϫ B cells into plasma cells was observed, although to a minor degree, in the presence of IL-4 ϩ CD40/CD32T. In this regard, we 9 and others 30 demonstrated that IgE can be produced by naive B cells in X-linked hyper-IgM syndrome patients. Thus, it is apparent that both CD27 ϩ memory and CD27 Ϫ naive B cells have the ability to produce IgE in response to IL-4 and enough CD40 signaling.…”