B-1 Cells: biological activity and importance in the implantation and metastatization of experimental murine melanoma cells

• Grant number: 03/01079-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2003
• End date: October 31, 2006
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Daniel Lopes
• Grantee: José Daniel Lopes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Although more than 20 years have passed since the discovery of B-1 cells, a large number of reports have been made in order to characterize and determine the origin and function of these cells. These efforts have sparked a good deal of controversy, little was added to better understand the role these cells might have on the modulation of pathologic phenomena such as inflammation. At least three B cell subsets, B-1 a, B-1 b and B-2 (conventional B cells) are present in the mouse periphery. B-1 cells constitute a minor fraction of B-cell population in spleen and Iymph nodes of mice. Nevertheless, they represent the main B-cell population in their peritoneal and pleural cavities. They express high levels of surface IgM, low levels of B220 and IgD, but not CD23, whereas conventional B-2 cells express high levels of B220 and IgD, CD23 and low levels of IgM. Although B-1 cells bear several features of B Iymphocytes, they also express characteristic surface markers of monocyte-derived macrophages such as low levels of Mac-1. Moreover, a subset designed B-1a have intermediate levels of CD5 on their surface. However, Mac-1 and CD5 antigens are lost when B-1 cells migrate out of the peritoneal cavity. Based on these characteristics, this cell lineage has been seen as a promiscuous lineage. Almeida et al demonstrated that B-1 cells spontaneously proliferate in stationary cultures of normal adherent mouse peritoneal cells. Additional experiments gave support for this conclusion since when peritoneal cells from Xid mice were cultivated, B-1 cells did not proliferate. As demonstrated in the literature, Xid mice have the production of B-1 Iymphocyte impaired. Further, B-1 cells migrate to a non-specific inflammatory focus and differentiated into a macrophage-like cell. Nevertheless, the role these cells might play on the kinetics and fate of the inflammatory response and on parasite infection is not yet fully established. However, Xid mice are significantly more resistant to T. cruzi, P. brasiliensis (Kipnis, pers commun) and Iymphatic filarial parasite infections. These data support the hypothesis that B-1 cells could down-regulate the efficacy of effector cells, such as macrophages, to eliminate parasites in the inflammatory milieu. Additionally, B-1 cells produce and utilize IL -10 as an autocrine growth factor and this cytokine is an important negative regulator of cell mediated immunity. In this direction, our group demonstrated that B-1 cells can influence effector functions of macrophages in vitro via IL-10 secretion. Here in we intend to demonstrate that B-1 cells exit celomatic cavities and migrate to an inflammatory site to transform into a novel type of mononuclear phagocyte. In addition, some aspects concerning the characterization of precursors of these cells and the mechanisms of their survival in culture will be addressed. Results will certainly bring new insights on the role these cells could play in inflammatory, degenerative and neoplasic pathologies. (AU)