Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibody-Producing Cells / immunology
-
Antigens, Protozoan / immunology
-
B-Cell Activating Factor
-
B-Lymphocytes / cytology
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
B-Lymphocytes / parasitology
-
CD11b Antigen / immunology*
-
Cell Differentiation / immunology
-
Cell Growth Processes / immunology
-
Chagas Disease / immunology*
-
Chagas Disease / parasitology
-
Cytokines / immunology
-
Cytokines / metabolism*
-
Female
-
Flow Cytometry
-
Glutamate Dehydrogenase / immunology
-
Immunoglobulin Isotypes / immunology
-
Interleukin-10 / genetics
-
Interleukin-10 / immunology
-
Interleukin-6 / genetics
-
Interleukin-6 / immunology
-
Lymphocyte Activation
-
Membrane Proteins / genetics
-
Membrane Proteins / immunology
-
Mice
-
Mice, Inbred BALB C
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
Trypanosoma cruzi / immunology*
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / immunology
Substances
-
Antigens, Protozoan
-
B-Cell Activating Factor
-
CD11b Antigen
-
Cytokines
-
Immunoglobulin Isotypes
-
Interleukin-6
-
Membrane Proteins
-
RNA, Messenger
-
Tnfsf13b protein, mouse
-
Tumor Necrosis Factor-alpha
-
Interleukin-10
-
Glutamate Dehydrogenase