A Trypanosoma cruzi antigen signals CD11b+ cells to secrete cytokines that promote polyclonal B cell proliferation and differentiation into antibody secreting cells.

MONTES C; ACOSTA RODRIGEZ E; MUCCI J; ZUÑIGA E; CAMPETELLA O; GRUPPI A

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Año: 2006 vol. 36 p. 1474 - 1485

0014-2980

Microbial-induced polyclonal activation of B cells is a common event in several forms of infections, and is believed to play a crucial role both for enhancing the production of specific antibodies and for maintenance of B cell memory. Therefore, a major challenge in biomedical research is the identification of pathogen-derived products capable of rapidly mounting B cell expansion and differentiation. Here we report that glutamate dehydrogenase (GDH) stimulates polyclonal proliferation and differentiation of naive B cells. This stimulation was found to be T cell independent, but to absolutely require CD11b(+) cells. Moreover, we demonstrate that stimulation of CD11b(+) cells by GDH leads to the production of IL-6, IL-10 and B cell-activating factor (BAFF), all of which combine to powerfully induce B cell expansion. Importantly, IL-6 and IL-10 further drive B cell terminal differentiation into plasma cells by up-regulating critical transcription factors and immunoglobulin secretion. Our data provide the first evidence that a protozoan antigen can induce BAFF production by accessory cells, which in concert with other cytokines trigger polyclonal B cell activation.