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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2312-2320
Phenotypic and functional characteristics of hematopoietic cell
lineages in CD69-deficient mice
Pilar Lauzurica,
David Sancho,
Miguel Torres,
Beatriz Albella,
Mónica Marazuela,
Teresa Merino,
Juan A. Bueren,
Carlos Martínez-A, and
Francisco Sánchez-Madrid
From the Departamento de Fisiología, Universidad de
Barcelona, Barcelona, Spain; Servicio de Inmunología, Hospital
de la Princesa, Universidad Autónoma de Madrid, Spain; Department
of Immunology and Oncology, Centro Nacional de Biotecnología,
CSIC-UAM, and Departamento de Biología Molecular y Celular.
CIEMAT. Madrid.
AIM/CD69 is the earliest leukocyte activation antigen and is
expressed mainly by activated T, B, and natural killer (NK) cells. It
is also constitutively expressed by platelets, by bone marrow myeloid
precursors, and by small subsets of resident lymphocytes in the
secondary lymphoid tissues. The engagement of CD69 by specific antibodies induces intracellular signals, including
Ca++ flux, cytokine synthesis, and cell proliferation.
To investigate the physiological relevance of CD69, we generated mice
deficient in CD69 (CD69-/-) by gene targeting in embryonic stem cells.
CD69 (-/-) mice showed largely normal hematopoietic cell development and normal T-cell subpopulations in thymus and periphery. Furthermore, studies of negative- and positive-thymocyte selection using a T-cell
receptor transgenic model demonstrated that these processes were not
altered in CD69 (-/-) mice. In addition, natural killer and cytotoxic T
lymphocyte cells from CD69-deficient mice displayed cytotoxic activity similar to that of wild-type mice. Interestingly, B-cell development was affected in the absence of CD69. The
B220hiIgMneg bone marrow pre-B cell compartment
was augmented in CD69 (-/-) mice. In addition, the absence of CD69 led
to a slight increase in immunoglobulin (Ig) G2a and IgM responses to
immunization with T-dependent and T-independent antigens. Nevertheless,
CD69-deficient lymphocytes had a normal proliferative response to
different T-cell and B-cell stimuli. Together, these observations
indicate that CD69 plays a role in B-cell development and suggest that
the putative stimulatory activity of this molecule on bone
marrow-derived cells may be replaced in vivo by other signal
transducing receptors.

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