Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation.

Dramatic changes in morphology and myelin protein expression take place during the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the differentiation process. Molecules that could induce Fyn signaling have not been studied. Such molecules are promising therapeutic targets in demyelinating diseases. We provide evidence that the common gamma chain of immunoglobulin Fc receptors (FcRgamma) is expressed in OPCs and has a role in triggering Fyn signaling. FcRgamma cross-linking by immunoglobulin G on OPCs promotes the activation of Fyn signaling and induces rapid morphological differentiation with upregulation of myelin basic protein (MBP) expression levels. Mice deficient in FcRgamma are hypomyelinated, and a significant reduction in MBP content is evident. Our findings indicate that the FcRgamma-Fyn-MBP cascade is pivotal during the differentiation of OPCs into myelinating oligodendrocytes, revealing an unexpected involvement of immunological molecules.

The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis.

BACKGROUND: The systemic anaphylaxis reaction comprises various symptoms, including hypotension, changes in respiration pattern, and hypothermia. OBJECTIVE: To elucidate the role of histamine in each of these symptoms, we induced the passive systemic anaphylaxis reaction in histidine decarboxylase gene knockout (HDC [-/-]) mice, which lack histamine. METHODS: HDC(-/-) mice were generated by knocking out the HDC gene, which codes for the unique histamine-synthesizing enzyme. Twenty-four hours after the injection of IgE, HDC(+/+) and HDC(-/-) mice were injected with allergen and body temperature, blood pressure, and respiratory function were monitored in each mouse. RESULTS: Blood pressure dropped in both the HDC(-/-) mice and the HDC(+/+) mice. In contrast, respiratory frequency dropped and the expiratory respiration time was elongated only in the HDC(+/+) mice. Body temperature was decreased in the HDC(+/+) mice and was practically unchanged in the HDC(-/-) mice. Histamine receptor antagonists blocked the body temperature drop in the HDC(+/+) mice. Intravenous histamine induced similar patterns of body temperature decrease in the HDC(+/+) mice and the HDC(-/-) mice. Mast cell-deficient W/W (v) mice did not show the decrease in body temperature; this suggests that the histamine that contributed to the decrease in body temperature was derived from mast cells. CONCLUSION: According to the results of this investigation, in the passive systemic anaphylaxis reaction, respiratory frequency, expiratory time, and body temperature are shown to be controlled by the activity of histamine, but its contribution to blood pressure is negligible.

Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice.

Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than those from wild-type mice upon B cell receptor ligation. T helper type 2 (T(H)2)-prone humoral responses were augmented in PIR-B(-/-) mice upon immunization with T-dependent antigens, including increased interleukin 4 and decreased interferon-gamma responses, as well as enhanced IgG1 and IgE production. Impaired maturation of dendritic cells (DCs), possibly due to perturbed intracellular signaling, was responsible for the skewed responses. Thus, PIR-B is critical for B cell suppression, DC maturation and for balancing T(H)1 and T(H)2 immune responses.