Functional Characterization of CBAP in Controlling Bim-independent Hematopoietic Homeostasis (97.14)

• Published in: The Journal of immunology (1950) Vol. 182; no. 1_Supplement; pp. 97 - 97.14
• Main Authors: Chiang, Yun-Jung, Yen, Jong-Young Jeffrey
• Format: Journal Article
• Language: English
• Published: 01.04.2009
• DOI: 10.4049/jimmunol.182.Supp.97.14
• ISSN: 0022-1767

Abstract The lifespan of hematopoietic cells is involved in controlling inflammation and autoimmune response. CBAP (Common Beta chain Associating Protein) is a newly annotated membrane bound protein and is identified to associate with Box II domain, highly conserved among cytokine receptor superfamily, of common beta chain (βc) of GM-CSF/IL-3/IL-5 receptor. In GM-CSF withdrawal-induced cell death assay, CBAP is demonstrated to trigger apoptotic signal, which is involved in Bax/Bak activation, and could be blocked by overexpression of Bcl-2 protein. In order to characterize the biological role of CBAP in vivo, we created the CBAP-deficient mice in either wild-type (wt) or Bim-deficient genetic background. We find that CBAP deficient mice are viable and fertile. The targeted allele could be transmitted according Mendel's Law inside the family, suggesting there is no apparent reproductive defect. In addition, we find the alterations of haematopoietic homeostasis. CBAP-deficiency increased the numbers of T cells, B cells and dendritic cells in the peripheral lymphatic organs in both the wt- and Bim-/- background, suggesting CBAP plays a non-redundant role in regulating hematopoietic homeostasis. CBAP-deficient primary bone marrow-derived dendritic cells (BMDCs) are more resistant to GM-CSF withdrawal-induced cell death, suggesting the contribution of CBAP in the regulation of apoptosis. Taken together, these results suggest the potential role of CBAP in controlling death of hematopoietic cells as well as playing a redundant role of Bim-regulated cell death.