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B Lymphocyte Response To Primary CMV Infection During Pregnancy

par Dauby, Nicolas ;Sartori, Delphine ;Haumont, Michèle ;Lecomte, Sandra ;Liesnard, Corinne ;donner, catherine ;Marchant, Arnaud
Référence (San Francisco), 4th Congenital Cytomegalovirus Conference
Publication Publié, 2012-10-29

Abstract de conférence

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Résumé :

Although neutralizing antibodies represent an essential component of protective immunity against CMV, the response of B lymphocytes to primary CMV infection remains poorly characterized. In a cohort of pregnant women diagnosed with primary infection and chronically infected healthy subjects, we characterized total memory B cell (MBC) populations as well as B cell responses to CMV glycoprotein B and tegument proteins pp150 and pp52. MBC frequencies and phenotype were assessed by flow cytometry. Antibody and B cell responses to CMV antigens were measured by ELISA and by B-cell ELISPOT usingrecombinant gB and pp150/pp52 polypeptides. Tetanus toxoid (TT) was used to assess bystander MBC activation. Activated memory B-cells (CD19+CD27+CD20+CD21low/-) were detected at higher frequencies during primary as compared to chronic infection and remained elevated for several months after diagnosis. Activated MBC expressed higher levels of the co-stimulatory molecules CD80 and CD86, of the proliferation marker Ki-67 and of the activation marker CD95 as compared to classical MBC (CD19+CD27+CD20+CD21+). Anti-gB IgG antibody levels were significantly lower in primary as compared to chronic infection and increased during the first months after diagnosis. In contrast, similar levels of anti-tegument IgG were detected in primary and chronic infection. The more progressive increase of anti-gB IgG did not appear to be related to a progressive expansion of antibody-secreting cells (ASC) as the highest frequencies of gB-specific ASC were detected at the time of diagnosis of primary infection. Anti-TT IgG levels decreased significantly and frequencies of TT-specific ASC remained constant during the first months after diagnosis of primary CMV infection, suggesting transient bystander B cell activation. In conclusion, primary CMV infection during pregnancy is associated with high frequencies of activated MBC that may include some bystander activation. B cell response to tegument proteins develop early during the course of primary infection whereas the capacity of gB-specific memory B cells to produce IgG may be acquired more progressively. Fluorescent antigen-labeling experiments are being conducted in order to further characterize gB- and tegument protein-specific B lymphocyte responses.