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Free keywords:
HEMATOPOIETIC STEM-CELLS; CYTOPLASMIC DOMAIN; KAPPA-B; DIFFERENTIAL
REQUIREMENTS; ADHESION MOLECULE-1; EPITHELIAL-CELLS; LINEAGE FATE;
BONE-MARROW; INTEGRIN; CD4Immunology; B- cell maturation; cell adhesion; ICAP-1; integrins; thymocyte
development;
Abstract:
ICAP-1 regulates beta 1-integrin activation and cell adhesion. Here, we used ICAP-1-null mice to study ICAP-1 potential involvement during immune cell development and function. Integrin alpha 4 beta 1-dependent adhesion was comparable between ICAP-1-null and control thymocytes, but lack of ICAP-1 caused a defective single-positive (SP) CD8(+) cell generation, thus, unveiling an ICAP-1 involvement in SP thymocyte development. ICAP-1 bears a nuclear localization signal and we found it displayed a strong nuclear distribution in thymocytes. Interestingly, there was a direct correlation between the lack of ICAP-1 and reduced levels in SP CD8(+) thymocytes of Runx3, a transcription factor required for CD8(+) thymocyte generation. In the spleen, ICAP-1 was found evenly distributed between cytoplasm and nuclear fractions, and ICAP-1(-/-) spleen T and B cells displayed upregulation of alpha 4 beta 1-mediated adhesion, indicating that ICAP-1 negatively controls their attachment. Furthermore, CD3(+)- and CD19(+)-selected spleen cells from ICAP-1-null mice showed reduced proliferation in response to T- and B-cell stimuli, respectively. Finally, loss of ICAP-1 caused a remarkable decrease in marginal zone B- cell frequencies and a moderate increase in follicular B cells. Together, these data unravel an ICAP-1 involvement in the generation of SP CD8(+) thymocytes and in the control of marginal zone B-cell numbers.
