Peritoneal CD5(+) B-1 cells have signaling properties similar to tolerant B cells

Wong, S.-C., Chew, W.-K., Tan, J. E.-L., Melendez, A. J., Francis, F. and Lam, K.-P. (2002) Peritoneal CD5(+) B-1 cells have signaling properties similar to tolerant B cells. Journal of Biological Chemistry, 277(34), pp. 30707-30715. (doi: 10.1074/jbc.M202460200) (PMID:12070149)

Abstract

CD5+ B (or B-1) cells are the normal precursors of B cell chronic lymphocytic leukemia. They differ from conventional B (B-2) cells with respect to their phenotype and mitogenic responses and are often secretors of the natural polyreactive antibodies in the serum. The origin of B-1 cells remains controversial, and the relationship between B-1 cells and autoreactive B cells is unclear. Here, we compare the signaling pathways that are activated by the engagement of the B cell antigen receptor (BCR) in B-1 and B-2 cells. Stimulation of the BCR leads to the induced activation of the three major classes of mitogen-activated protein kinases (MAPKs), ERK, JNK, and p38 MAPK, as well as the Akt kinase and the transcription factors nuclear factor of activated T cells (NF-AT) and NF-κB in B-2 cells. In contrast, B-1 cells have constitutive activation of ERK and NF-AT but exhibit delayed JNK and lack p38 MAPK and NF-κB induction upon BCR cross-linking. The lack of NF-κB activation in B-1 cells may be due to a lack of Akt activation in these cells. Furthermore, our study using specific inhibitors reveals that the extended survival of B-1 cells in culture is not due to the constitutive activation of ERK; nor is it due to Akt signaling or Bcl-xL up-regulation, since these are not induced in B-1 cells. The current findings of altered MAPK and NF-AT activation and lack of NF-κB induction in B-1 cells indicate that these cells have signaling properties similar to tolerant B cells that are chronically exposed to self-antigens. Indeed, BCR stimulation of B-1 cells does not lead to their full activation as indicated by their lack of maximal up-regulation of specific markers such as CD25, CD69, and CD86.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Melendez Romero, Dr Alirio
• Authors: Wong, S.-C., Chew, W.-K., Tan, J. E.-L., Melendez, A. J., Francis, F., and Lam, K.-P.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J Biol Chem.
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Published Online: 17 June 2002
• Published Online: 17 June 2012