IAI Accepts, published online ahead of print on 26 October 2009

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Infect. Immun. doi:10.1128/IAI.00868-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Development of IgM memory to both a T cell-independent and a T cell-dependent antigen following infection with Vibrio cholerae O1 in Bangladesh

Emily A. Kendall, Abdullah A. Tarique, Azim Hossain, Mohammad Murshid Alam, Mohammad Arifuzzaman, Nayeema Akhtar, Fahima Chowdhury, Ashraful I. Khan, Regina C. LaRocque, Jason B. Harris, Edward T. Ryan, Firdausi Qadri, and Stephen B. Calderwood^*

International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts; Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts

^* To whom correspondence should be addressed. Email: scalderwood{at}partners.org.

Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B cells of the IgG and IgA isotypes to V. cholerae O1 antigens including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB) has been demonstrated following cholera. Memory B cells of the IgM isotype may play a role in long-term protection, particularly against T cell-independent antigens, but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we assayed acute and convalescent blood samples from 32 cholera patients for the presence of memory B cells that produce cholera-antigen-specific IgM antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and antibody-secreting-cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.