Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice.
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.
Takai
T
T
Department of Biotechnology, Faculty of Engineering, Okayama University, Japan.
Ono
M
M
Hikida
M
M
Ohmori
H
H
Ravetch
J V
JV
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D015550:Cell Degranulation; D002460:Cell Line; D018390:Gene Targeting; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D017452:Receptors, IgG