Boston University Medical Campus
Microbiology

Professor of Microbiology

B.S. Duke University
Ph.D. Duke University

Our laboratory is interested in the relationship between innate and adaptive immunity, and how components of the two discrete systems interact to generate long-lasting protective immune responses. Our research focuses on three major areas.

The first area focuses on IgM antibodies as efficient bridges of innate and adaptive immunity. We are interested in the role of IgM antibodies as innate molecules that promote adaptive immune responses when complexed with cognate antigen. Mice that are deficient in secreted IgM have a number of immune defects characterized by their inability to respond to low concentrations of protein antigens, delayed production of protective antibody responses to pathogens, and delayed germinal center formation. In the absence of secreted IgM, pathogens fail to concentrate into secondary lymphoid organs and instead disseminate into vital organs. The adjuvant activity of IgM is complement dependent and, consequently, mice deficient in components of the classical complement pathway or in the complement receptors CR1/2 (CD21/35) have defects similar to those observed in secreted IgM-deficient mice. Because specific IgM enhances immune responses to particulate and soluble antigens, the defects in adaptive immune responses in mice deficient in secreted IgM can be attributed to the failure of other secreted antibody isotypes to compensate for IgM function. We have demonstrated an “adjuvant” role for IgM, and characterized some of the mechanisms by which IgM enhances adaptive immunity. The function of IgM can be attributed, at least in part, to its ability to concentrate immune complexes in the foci of the spleen, where innate B cells in the marginal zones traffic the complexes to follicular dendritic cells, stromal elements that promote efficient germinal center formation. Related to this, we have been investigating the effect traumatic injury has on adaptive humoral responses. Following several types of injury, the humoral immune system is often compromised, but the mechanisms are poorly understood. We have found that following such trauma, IgM fails to act as an adjuvant in priming immune responses, and we are focusing on changes in the uptake and processing of these complexes in splenic follicles as a major consequence leading to immune suppression.

Another interest of the laboratory, undertaken in collaboration with Ann Marshak-Rothstein and Greg Viglianti of this department, involves studies of the role that Toll-like receptors (TLRs) play in the activation of autoimmune B lymphocytes. We are interested in understanding how, and what intracellular compartment(s), ligands for intracellular TLRs, especially TLR9, intersect with these receptors in B cells, and the consequences of these interactions for the fate of the B cell and for B cell functions.

Finally, the laboratory is focusing on the immune consequences of infection with highly pathogenic hemorrhagic fever viruses, including filoviruses. Patients infected with these viruses often fail to make adaptive immune responses and succumb to infection. While this is often attributed to dysfunctional innate immune responses, the nature of the defects in immune responses to these viruses is poorly understood. We have initiated studies to dissect the early immune responses to these viruses, understand how they affect the ability of infected animals to initiate adaptive immune responses, and identify the components of infection that lead to the cytokine storms that characterize infection with these viruses.

Representative Publications

1. Youd, M.E., A.R. Ferguson, and R.B. Corley. 2002. Synergistic roles of IgM and complement in antigen trapping and follicular localization. Eur. J. Immunol. 32:2328-2337.
2. Flemming, J.A., K.H. Perkins, L. Luus, A.R. Ferguson and R.B. Corley. 2004. Disruption of membrane cholesterol stimulates MyD88-dependent NF-kappaB activation in immature B cells. Cell. Immunol. 229:68-77.
3. Ferguson, A.R., M.E. Youd, and R. B. Corley. 2004. Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells. Int. Immunol. 16:1411-1422.
4. Youd, M.E., L. Luus, and R.B. Corley. 2004. IgM monomers accelerate disease manifestations in autoimmune-prone fas-deficient mice. J. Autoimmunity 23:333-343.
5. Doerre, S., K. Perkins Mesires, K.M. Daley, T. McCarty, S. Knoetig and R.B. Corley. 2005. Reductions in IkappaBepsilon and changes in NF-kappaB activity during B lymphocyte differentiation. J. Immunol. 174:983-991.
6. Ferguson, A.R. and R.B. Corley. 2005. Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-kappaB p50-deficient mice. BMC Immunology 6:8 (18 April, 2005).
7. Corley, A.R., E.M. Morehouse and A.R. Ferguson. 2005. IgM accelerates affinity maturation. Scand. J. Immunol. 62 (suppl 1): 55-61.
8. Busconi, L., J.W. Bauer, J.R. Tumang, A. Laws, K. Perkins-Mesires, A.S. Tabor, C. Lau, R.B. Corley, T.L. Rothstein, F.E. Lund, T.W. Behrens, A. Marshak-Rothstein. 2007. Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and Toll-like Receptor 9. J. Immunol. 179: 7397-7405.
9. Yasuda, K., C. Richez, M.B. Uccellini, R.J. Richards, S. Akira, M. Monestier, R.B. Corley, G.A. Viglianti, A. Marshak-Rothstein, and I.R. Rifkin. 2009. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing complexes. (submitted for publication).

Books and Book Chapters

1. Corley, R.B. 2004. Chapter 6. Antibodies. In: Immunology, Infection, and Immunity: An Introductory Text (pp 113-143). Edited by G.B. Pier, J.B. Lyczak and L.M. Wetzler, ASM Press, Washington, DC.
2. Corley, R.B. 2005. A Guide to Methods in the Biomedical Sciences. Springer Science+Business Media, Inc., New York, NY.

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