Abstract

Abstract Aim: Administration of vaccine via nasal route has many merits including induction of cross-protective IgA on the surface of respiratory mucosa. However there is little information about IgA producing cells in the nasal mucosa. We examined role of B-1 cells in nasal vaccination because B-1 cells are responsible for production of natural antibodies which possess wide reactivity to various pathogens. Results: B-1 cell deficient BtkKO mice and control were anesthetized and intranasally administrated with influenza HA vaccine with poly(I:C) as an adjuvant twice in 2-week interval. 2 weeks later, BtkKO mice showed significantly reduced anti-HA nasal IgA response compared to control. In contrast, when splenocytes from vaccinated mice were re-stimulated with inactivated influenza virus, cells from BtkKO mice showed same or higher response than controls in the terms of Th1 cytokine production and IFN-γ secreting cell number. Further, reconstitution of B-1 cells in the BtkKO mice resulted in partial recovery of Ig response to vaccination. Discussion: Although Btk is expressed not only in B cells but also in myeloid cells including dendritic cells, defect of B-1 cells should be responsible for the reduced nasal Ig response in the BtkKO mice because T cells in these mice were properly activated. Thus B-1 cells and their unknown regulators will be good target of potent nasal vaccine adjuvant.

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