title: Protective intestinal anti-rotavirus B cell immunity is dependent on alpha 4 beta 7 integrin expression but does not require IgA antibody production.
abstract: Rotavirus (RV) is the main cause of severe gastroenteritis in young children; protection has been correlated with intestinal Ab responses. Using a mouse model of RV infection and beta(7)-deficient (beta(7)(-/-)) mice, which do not express alpha(4)beta(7) integrin, we demonstrated the importance of alpha(4)beta(7) integrin in B cell-mediated anti-RV immunity. beta(7)(-/-) mice acutely infected with murine RV resolved infection and developed normal serum IgG Abs but had diminished intestinal IgA responses. alpha(4)beta(7)(-/-) immune B cells did not resolve RV infection when adoptively transferred into RV-infected Rag-2-deficient mice. Fewer RV-specific B cells were found in the intestine of Rag-2-deficient mice transferred with beta(7)(-/-) B cells compared with wild type. The absence of alpha(4)beta(7) expression and/or a lower frequency of IgA-producing cells among transferred beta(7)(-/-) B cells could have accounted for the inability of these cells to resolve RV infection following passive transfer. To distinguish between these possibilities, we studied the importance of IgA production in RV infection using IgA-deficient (IgA(-/-)) mice. IgA(-/-) mice depleted of CD8(+) T cells were able to clear primary RV infection. Similarly, adoptive transfer of immune IgA(-/-) B cells into chronically infected Rag-2-deficient mice resolved RV infection. We further demonstrated in both wild-type and IgA(-/-) mice that, following oral RV infection, protective B cells reside in the alpha(4)beta(7)(high) population. Our findings suggest that alpha(4)beta(7) integrin expression is necessary for B cell-mediated immunity to RV independent of the presence of IgA.
authors.affiliation: Department of Microbiology and Immunology, Palo Alto Health Care System, Palo Alto, CA 94305, USA. nelly-kuklin@merck.com
authors.forename: N A
authors.initials: NA
authors.lastname: Kuklin
authors.forename: L
authors.initials: L
authors.lastname: Rott
authors.forename: N
authors.initials: N
authors.lastname: Feng
authors.forename: M E
authors.initials: ME
authors.lastname: Conner
authors.forename: N
authors.initials: N
authors.lastname: Wagner
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.forename: H B
authors.initials: HB
authors.lastname: Greenberg
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology*; D002469:Cell Separation; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007072:Immunoglobulin D / Q000096:biosynthesis; D007156:Immunologic Memory / Q000235:genetics; D016023:Integrins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D007399:Interphase / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage; D017201:Virus Shedding / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D016023:Integrins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D014765:Viral Vaccines; C071777:integrin alpha4beta7; D017493:Leukocyte Common Antigens