Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production induced by anti-CD58 monoclonal antibody.

Abstract

We studied the effects of histamine on human immunoglobulin (IgE) and IgG4 production. Histamine selectively enhanced IgE and IgG4 production in purified surface IgE and IgG4 negative (sIgE-sIgG4-) B cells from normal donors stimulated with interleukin (IL)-4 plus anti-CD58 or IL-13 plus anti-CD58 monoclonal antibody (mAb) without affecting production of IgG1, IgG2, IgG3, IgM, IgA1, or IgA2. In cultures with IL-4 plus anti-CD58 mAb, histamine-induced enhancement of IgE and IgG4 production was specifically blocked by thioperamide (H3 receptor antagonist), and was inhibited by anti-IL-10 antibody (Ab). In contrast, in cultures with IL-13 plus anti-CD58 mAb, histamine-induced enhancement was blocked by dimaprit (H1 receptor antagonist), and was inhibited by anti-IL-6 mAb. Histamine also enhanced IgE and IgG4 production by in vivo-generated sIgE+ and sIgG4+ B cells, respectively, from atopic patients; enhancement was blocked by dimaprit and thioperamide, and was inhibited by anti-IL-6 mAb and anti-IL-10 Ab. In sIgE-sIgG4- B cells, IL-4 plus anti-CD58 mAb induced IL-10 production and IL-10 receptor expression, whereas IL-13 plus anti-CD58 mAb induced IL-6 production and IL-6 receptor expression. Histamine increased IL-10 and IL-6 production without affecting IL-10 and IL-6 receptor expression, in cultures with IL-4 plus anti-CD58 mAb and with IL-13 plus anti-CD58 mAb, respectively, which was blocked by thioperamide and dimaprit, respectively. In contrast, sIgE+ and sIgG4+ B cells spontaneously produced both IL-6 and IL-10 and constitutively expressed IL-6 and IL-10 receptors, and histamine increased IL-6 and IL-10 production without affecting IL-6 or IL-10 receptor expression, which was blocked by thioperamide and dimaprit. These results indicate that histamine enhanced IgE and IgG4 production by increasing endogenous IL-6 and IL-10 production via H1 and H3 receptors, respectively.

Initial High-Dose Nasal Allergen Exposure Prevents Allergic Sensitization to a Neoantigen

“…We observed a positive correlation between IgG4 and IgE levels within the low-and medium-dose groups, with the size of the IgE:IgG4 ratio similar for IgE responders in both groups. This is consistent with previous observations that allergic patients often produce high levels of allergen-specific IgG4 (29,30) and considerable evidence that IgE and IgG4 share common molecular regulatory mechanisms (31)(32)(33)(34). However, we also noted a "disparity" in IgG4 and IgE levels, i.e., elevated IgG4 and undetectable IgE, for approximately half of the medium-dose subjects and the vast majority of high-dose subjects (Fig.…”

Histamine H4and H2Receptors Control Histamine-Induced Interleukin-16 Release from Human CD8+T Cells

“…Taking their opposite adenylyl cyclase coupling into consideration, an additive effect or synergism between H 2 (leading to cAMP elevation) and H 4 (leading to decrease of cAMP) was not expected. Rather, histamine seems to regulate IL-16 liberation from CD8 ϩ cells by acting in parallel on various of its receptors, an observation made for this biogenic amine in several of its immune functions (Kimata et al, 1996;Sirios et al, 2000;Caron et al, 2001).…”

“…This puts many observations made in the past with thioperamide, previously only known as an H 3 antagonist, into a different perspective, since nearly all relevant findings using thioperamide in the immune system may be attributed to H 4 rather that to H 3 . Among those putatively H 4 -mediated immune functions of histamine are the inhibition of tumor necrosis factor release from mast cells (Bissonnette, 1996), stimulation of IL-10 in monocytes (Sirios et al, 2000), Ca 2ϩ mobilization in human eosinophils (Raible et al, 1994), and IgE production from IL-4 ϩ anti-CD58/LFA3-antibody stimulated human B cells (Kimata et al, 1996). However, alveolar macrophages, a population not studied here, were reported to express H 3 mRNA (Sirios et al, 2000), and therefore a role of H 3 in the immune system of the lung cannot be excluded.…”

Molecular Identification of IgE-Dependent Histamine-Releasing Factor as a B Cell Growth Factor

“…Histamine induces B cell proliferation in the presence of anti-IgM Ab only when the serum was dialyzed and c-Kit-positive cells were removed (32). It enhances IgE and IgG4, but has no effect on IgG, IgM, or IgA production in the presence of IL-4 or IL-13 (33). Based on the culture conditions and Ig production patterns, it is unlikely that the effects of rHRF on B cell activities in this study are due to the indirect effects of histamine production.…”