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Nasal Cholera Toxin Up‐regulates Mucosal DCs And B1 B Cells Interactions For The Induction Of Innate IgA CSR.
Author(s) -
KATAOKA KOSUKE,
Fujihashi Keiko,
Sekine Shinichi,
Kobayashi Ryoki,
Sims Rebekah,
Ito Hiroo,
McGhee Jerry R,
Shizukuishi Satoshi,
Fujihashi Kohtaro
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.853.12
Subject(s) - cholera toxin , immunology , receptor , nasal administration , adjuvant , chemistry , biology , medicine , microbiology and biotechnology
Our previous study showed that nasal immunization with TNP‐LPS plus cholera toxin (CT) as mucosal adjuvant elicited increased levels of mucosal TNP‐LPS‐specific secretory (S)‐IgA Ab responses through an IL‐5‐IL‐5 receptor interplay between CD4 + T cells and B1a B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Thus, RT‐PCR assay revealed that NALT, NPs and SMGs of mice given nasal TNP‐LPS plus CT contained AID, αCT and Iμ‐Cα transcripts. In this study, we tested our hypothesis that DCs play a central role in the induction of IgA class switching recombination (CSR) by mucosal B1 B cells for the enhancement of T cell‐independent S‐IgA Ab responses. When cells from NPs and SMGs were subjected to flow cytometric analysis, DCs of mice given nasal TNP‐LPS plus CT expressed higher levels of co‐stimulatory molecules than those of mice given TNP‐LPS alone, even though the numbers of DCs in NPs and SMGs were unchanged. Interestingly, higher levels of APRIL‐specific mRNA was expressed by DCs in NPs and SMGs, while B cells in SMGs and NPs showed significant levels of TACI‐ and BCMA‐specific mRNA. These findings suggest that DCs activated by nasal CT induce B cell IgA CSR through TACI and APRIL/BMCA interactions. This work is supported by NIH grants DE 12242, AG 025873, AI 18958 and AI 043197 as well as by Grants‐in‐Aid (C‐17592179, C‐19592403) from the Ministry of Education, Culture, Sports and Science of Japan.