Human immunoglobulin A receptor (FcαRI, CD89) function in transgenic mice requires both FcR γ chain and CR3 (CD11b/CD18)

Even though more immunoglobulin A (IgA) is produced in humans than all other isotypes combined, relatively little is known about receptors that bind the Fc part of IgA. The myeloid IgA receptor, Fc alpha RI (CD89), triggers various effector functions in vitro, but its in vivo role remains unclear. Here, a transgenic mouse model is described in which Fc alpha RI is expressed under its own regulatory sequences, Receptor expression and regulation by cytokines was comparable to the human situation and hFc alpha RI can trigger phagocytosis and lysis of tumor cells, To analyze the contribution of the FcR gamma chain or the beta 2 integrin CR3 (CD11b/CD18) in Fc alpha RI biological function, Fc alpha RI transgenic mice were crossed with either FcR gamma chain -/- or CR3 -/- mice. In contrast to in vitro data, FcR gamma chain was essential for surface expression of hFc alpha RI in vivo, Functional studies in hFc alpha RI/gamma-/-mice were, therefore, limited. In vitro studies showed FcR gamma chain to be necessary for phagocytosis. Neither hFc alpha RI expression nor phagocytosis, triggered via hFc alpha RI, were influenced by CR3. Remarkably, the capacity to lyse tumor targets was ablated in hFc alpha RI transgenic/CR3-/- mice, although binding of neutrophils to tumor cells was intact. This shows a previously unrecognized importance of CR3 for hFc alpha RI-mediated antibody-dependent cellular cytotoxicity (ADCC). (C) 1999 by The American Society of Hematology.