Augmented humoral and anaphylactic responses in FcγRII-deficient mice

• Published in: Nature (London) Vol. 379; no. 6563; pp. 346 - 349
• Main Authors: Takai, Toshiyuki, Ono, Masao, Hikida, Masaki, Ohmori, Hitoshi, Ravetch, Jeffrey V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 25-01-1996
• Subjects: Animals; Antibodies - immunology; Antibody Formation; B-Lymphocytes - immunology; Biological and medical sciences; Cell Degranulation; Cell Line; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Immunobiology; Mast Cells - immunology; Mice; Modulation of the immune response (stimulation, suppression); Passive Cutaneous Anaphylaxis - immunology; Receptors, IgG - deficiency; Receptors, IgG - genetics; Receptors, IgG - immunology; Allergy; Immune response; Immunomodulation; Rodentia; IgG; Immune deficiency; Vertebrata; Mammalia; Anaphylaxis; Mouse; Degranulation; Mast cell; Humoral immunity; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/379346a0

Despite its widespread distribution on both lymphoid and myeloid cells, the biological role of the low-affinity immunoglobulin-G receptor, Fc gamma RII, is not fully understood. Defects in this receptor or its signalling pathway in B cells result in perturbations in immune-complex-mediated feedback inhibition of antibody production. We now report that Fc gamma RII-deficient animals display elevated immunoglobulin levels in response to both thymus-dependent and thymus-independent antigens. Additionally, the effector arm of the allergic response is perturbed in these mice. Mast cells from Fc gamma RII-/- are highly sensitive to IgG-triggered degranulation, in contrast to their wild-type counterparts. Fc gamma RII-deficient mice demonstrate an enhanced passive cutaneous analphylaxis reaction, the result of a decreased threshold for mast-cell activation by Fc gamma RIII cross-linking. These results demonstrate that Fc gamma RII acts as a general negative regulator of immune-complex-triggered activation in vivo for both the afferent and efferent limbs of the immune response. Exploiting this property offers new therapeutic opportunities for the treatment of allergic and autoimmune disorders.