Research Bio
Overview
Virus-specific antibodies play a key role in providing a protective barrier to infection and in facilitating viral clearance once an infection is established. Antibody-producing cells or plasma cells are generated from B cells that divide and differentiate following recognition of specific antigen. A critical requirement for optimal antibody responses is the cognate help delivered to activated B cells by CD4 T cells. This help is important for directing antibody isotype switching in B cells, the process by which B cells switch from expressing IgM to expressing alternative isotypes (such as IgG1, IgG2a, and IgA in the mouse) with different functional characteristics. In addition, cognate T cell help is critical if activated B cells are to participate in germinal center reactions, where affinity maturation of the antibody response takes place and the cellular elements of B cell memory are generated. These elements include long-lived plasma cells, which maintain high levels of protective antibodies, and a population of memory B cells that will respond with rapid antibody production on re-exposure to cognate antigen. This brief overview grossly simplifies a remarkable and complex process that is regulated at many levels in ways that modulate the kinetics, magnitude, and quality of the acute B cell response, as well as characteristics of dispersed plasma cell and memory B cell populations. In general terms, our research is aimed at understanding the characteristics of optimally effective B cell responses and applying this knowledge towards the improvement of vaccination regimens.
Specific Research Interests
Our specific research focus is the B cell response to viruses that infect the respiratory tract (with an emphasis on influenza virus) and to vaccination regimens designed to generate B cell-mediated protection against these viruses. Particular research interests include: (i) regulation of the acute B cell response to infection and vaccination and the differentiation pathways that generate B cell memory and virus-neutralizing antibodies, (ii) aspects of B cell memory (plasma cells, memory B cells) in the respiratory tract, including mechanisms of localization, role in protection, and relationship to form of immunization, and (iii) regulation of IgA production and the establishment of antibody-mediated protection at mucosal surfaces.
2014 Jan
Alam S, Knowlden ZA, Sangster MY, Sant AJ. "CD4 T cell help is limiting and selective during the primary B cell response to influenza virus infection." Journal of virology.. 2014 Jan; 88(1):314-24. Epub 2013 Oct 23. |
2013 Jun
Sangster MY, Baer J, Santiago FW, Fitzgerald T, Ilyushina NA, Sundararajan A, Henn AD, Krammer F, Yang H, Luke CJ, Zand MS, Wright PF, Treanor JJ, Topham DJ, Subbarao K. "B cell response and hemagglutinin stalk-reactive antibody production in different age cohorts following 2009 H1N1 influenza virus vaccination." Clinical and vaccine immunology : CVI.. 2013 Jun; 20(6):867-76. Epub 2013 Apr 10. |
2013 Jan 15
He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB. "Heterovariant cross-reactive B-cell responses induced by the 2009 pandemic influenza virus A subtype H1N1 vaccine." The Journal of infectious diseases.. 2013 Jan 15; 207(2):288-96. Epub 2012 Oct 29. |
2012
Sundararajan A, Huan L, Richards KA, Marcelin G, Alam S, Joo H, Yang H, Webby RJ, Topham DJ, Sant AJ, Sangster MY. "Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization." PloS one. 2012 7(3):e34377. Epub 2012 Mar 23. |
2011 Nov 22
Sharma S, Sundararajan A, Suryawanshi A, Kumar N, Veiga-Parga T, Kuchroo VK, Thomas PG, Sangster MY, Rouse BT. "T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses." Proceedings of the National Academy of Sciences of the United States of America.. 2011 Nov 22; 108(47):19001-6. Epub 2011 Nov 03. |
