Phenotypic and functional characteristics of hematopoietic cell lineages in CD69-deficient mice

AIM/CD69 is the earliest leukocyte activation antigen and is expressed main ly by activated T, B, and natural killer (NK) cells. It is also constitutiv ely expressed by platelets, by bone marrow myeloid precursors, and by small subsets of resident lymphocytes in the secondary lymphoid tissues. The eng agement of CD69 by specific antibodies induces intracellular signals, inclu ding Ca++ flux, cytokine synthesis, and cell proliferation. To investigate the physiological relevance of CD69, we generated mice deficient in CD69 (C D69-/-) by gene targeting in embryonic stem cells. CD69 (-/-) mice showed l argely normal hematopoietic cell development and normal T-cell subpopulatio ns in thymus and periphery. Furthermore, studies of negative- and positive- thymocyte selection using a T-cell receptor transgenic model demonstrated t hat these processes were not altered in CD69 (-/-) mice. In addition, natur al killer and cytotoxic T lymphocyte cells from CD69-deficient mice display ed cytotoxic activity similar to that of wildtype mice. Interestingly, B-ce ll development was affected in the absence of CD69, The B220(hi)IgM(neg) bo ne marrow pre-B cell compartment was augmented in CD69 (-/-) mice. In addit ion, the absence of CD69 led to a slight increase in immunoglobulin (Ig) G2 a and IgM responses to immunization with T-dependent and T-independent anti gens. Nevertheless, CD69-deficient lymphocytes had a normal proliferative r esponse to different T-cell and B-cell stimuli. Together, these observation s indicate that CD69 plays a role in B-cell development and suggest that th e putative stimulatory activity of this molecule on bone marrow-derived cel ls may be replaced in vivo by other signal transducing receptors, (Blood. 2 000;95:2312-2320) (C) 2000 by The American Society of Hematology.