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Characterization and role of B1 cells in experimental models: murine melanoma and Paracoccidioides brasiliensis infection

Grant number: 07/51501-9
Support Opportunities:Research Projects - Thematic Grants
Start date: September 01, 2007
End date: August 31, 2010
Field of knowledge:Biological Sciences - Immunology - Applied 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

A large number of reports have been made in order to characterize and determine the origin and function of B-1 cells. At least three B cell subsets, B-1a, B-1b and B-2 (conventional B cells) are present in the mouse periphery. B1 cells 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-1 a 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. These cells might play a role on the kinetics and fate of the inflammatory response and on parasite infection. Xid mice, that have impaired production of B-1 lymphocyte, are significantly more resistant to T cruzi, P. brasiliensis (Kipnis, pers commun) and lymphatic filarial parasite infections. These data support the hypothesis that B-1 cells could down-regulate the efficacy of effectors 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 effectors functions of macrophages in vitro via IL-10 secretion. The role of these cells in the melanoma metastatic potential was demonstrated in vitro. B16F10 co-cultivated with B1 cells have increased expression of adhesion and protease molecules. Besides that, non-tumorigenic immortalized melanocytes (melan-a) co-cultivated with B1 cells for 72 hours were able to form tumors in mice. Herein we intend to demonstrate the importance of B-1 cells in melanoma and paracoccidioidomycosis, as well as evaluated their role in inflammation, autoimmunity and tolerance. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
XANDER, PATRICIA; NOVAES E BRITO, RONNI ROMULO; PEREZ, ELIZABETH CRISTINA; POZZIBON, JAQUELINE MACIEL; DE SOUZA, CAMILA FERREIRA; PELLEGRINO, RENATA; BERNARDO, VIVIANE; JASIULIONIS, MIRIAM GALVONAS; MARIANO, MARIO; LOPES, JOSE DANIEL. Crosstalk between B16 melanoma cells and B-1 lymphocytes induces global changes in tumor cell gene expression. Immunobiology, v. 218, n. 10, p. 1293-1303, . (07/51501-9)
LOPES, JOSE DANIEL; MARIANO, MARIO. B-1 cell: the precursor of a novel mononuclear phagocyte with immuno-regulatory properties. Anais da Academia Brasileira de Ciências, v. 81, n. 3, p. 489-496, . (07/51501-9, 04/08506-1)
PUGLIESE, LIVIA SOUZA; GONCALVES, THAIS OLIVEIRA; POPI, ANA FLAVIA; MARIANO, MARIO; PESQUERO, JOAO BOSCO; LOPES, JOSE DANIEL. B-1 lymphocytes differentiate into functional osteoclast-like cells. Immunobiology, v. 217, n. 3, p. 336-344, . (07/51501-9)