The Early Protective Thymus-Independent Antibody Response to Foot-and-Mouth Disease Virus Is Mediated by Splenic CD9! B Lymphocytes

OSTROWSKI, M; VERMEULEN, M; ZABAL, O; ZAMORANO, P.I; SADIR, AM; GEFFNER, J.R.; LOPEZ, O.J

JOURNAL OF VIROLOGY

Año: 2007 p. 9357 - 9367

0022-538X

Infection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specificthymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shownthat FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9! B lymphocytes to rapidly(3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration.In contrast, neither follicular (CD9") B lymphocytes from the spleen nor B lymphocytes from lymph nodesefficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizingantibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9! cell-derived IL-10 secretion. Incomparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating Blymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDVantibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruptionof the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody responsein infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediatedmodulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protectiveTI antibody response against this virus.