Human immunoglobulin A receptor (Fc alpha RI, CD89) function in transgenicmice requires both FcR gamma chain and CR3 (CD11b/CD18)

Even though more immunoglobulin A (IgA) is produced in humans than all othe r isotypes combined, relatively little is known about receptors that bind t he Fc part of IgA. The myeloid IgA receptor, Fc alpha RI (CD89), triggers v arious effector functions in vitro, but its in vivo role remains unclear. H ere, a transgenic mouse model is described in which Fc alpha RI is expresse d under its own regulatory sequences, Receptor expression and regulation by cytokines was comparable to the human situation and hFc alpha RI can trigg er phagocytosis and lysis of tumor cells, To analyze the contribution of th e FcR gamma chain or the beta 2 integrin CR3 (CD11b/CD18) in Fc alpha RI bi ological function, Fc alpha RI transgenic mice were crossed with either FcR gamma chain -/- or CR3 -/- mice. In contrast to in vitro data, FcR gamma c hain was essential for surface expression of hFc alpha RI in vivo, Function al studies in hFc alpha RI/gamma-/-mice were, therefore, limited. In vitro studies showed FcR gamma chain to be necessary for phagocytosis. Neither hF c alpha RI expression nor phagocytosis, triggered via hFc alpha RI, were in fluenced 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 (AD CC). (C) 1999 by The American Society of Hematology.