Análisis de la expresión de receptores de quimioquinas en linfocitos de ratones deficientes en proteína asociada al dominio citoplásmico de integrinas 1 (ICAP-1)

The integrin cytoplasmic domain–associated protein-1 (ICAP-1) is a protein that binds to the cytoplasmic domain of the b subunit of the b1 integrins, and hinders the interaction of these integrins with their activators such as talin and kindlin. In addition, ICAP-1 possesses a nuclear localization signal that allows it to shuttle to the nucleus, potentially being able to regulate gene transcription. In order to determine the specific role of ICAP- 1 in the migration and differentiation of immune cells, ICAP-1 knock-out mice were previously used. We show here that the observed reduction in the number and frequency of B lymphocytes from the spleen marginal zone (MZB) of ICAP-1-/- mice was independent of an anomalous localization in the follicles of lymph nodes (LNs). As the absence of ICAP-1 caused differences in the proportion of lymphocytes in the LNs, we studied whether the expression of the chemokine receptors CXCR5, CXCR4 and CCR7, as well as the levels of S1PR1 on these lymphocytes could be affected, which in turn could alter their localization. We observed that CXCR4 expression was significantly reduced on CD19+ B cells and on T CD4+ lymphocytes. We analyzed also, in vivo, the degree of apoptosis of B lymphocytes in the spleen of ICAP-1-/- mice. Our preliminary results revealed that follicular B lymphocytes from ICAP-1-null mice display a reduced apoptosis compared with wild type mice. Finally, we show that the lack of ICAP-1 does not alter the expression in the spleen of VCAM-1, a ligand of the a4b1 integrin which plays important roles in MZB cell localization. Together these data will contribute to a better knowledge of ICAP-1-dependent functions on immune cell development and trafficking.