Patrick C. Wilson, Ph.D.

APPOINTMENTS

  • Associate Professor, Department of Medicine - Section of Rheumatology, Knapp Center for Lupus and Immunology Research, Committee on Immunology

EDUCATION

Postdoctoral Training, The Rockefeller University

Ph.D.,  University of Texas Southwestern Medical Center, 2000

BA/MS, Youngstown State University, 1994

CONTACT INFORMATION

The University of Chicago
Jules F. Knapp Building
924 East 57th Street, R414
Chicago, Illinois  60637

wilsonp@uchicago.edu

Phone: (773) 702-9009

RESEARCH SUMMARY

B Cell Immunity and Autoimmunity: B Cells in Health and Disease

With a particular emphasis on antibody specificity, two primary interests have emerged in the lab: We study the fate and differentiation of autoreactive B cells and we characterize the human B cell response to infectious diseases. We combine the use of powerful mouse models of B cell selection with various clinical partnerships to link observations in laboratory models to the direct study of human B cell biology. 

B cell selection in the context of receptor editing: The random nature of antibody gene production leads to unavoidable autoreactivities that are avoided by either receptor editing (to change the B cell specificity) or by culling the offensive cells from the repertoire by deletion or inactivation.  Further adaptation of B cell specificity by somatic hypermutation can lead to both new autoreactive B cells or to high affinity autoantibodies that cause diseases such as lupus and arthritis. Our recent work has demonstrated that the very processes protecting us from autoreactive B cells can rather lead to the unforeseen inclusion of autoreactive B cells in the functional repertoire. Specifically, we found that receptor editing causes up to 10% of mouse B cells to express two antibody kappa variable gene alleles simultaneously. Presumably, in most cases one of these two alleles encodes an autoantibody, posing a threat for susceptible individuals.  We are therefore interested in learning the fate of these cells and their consequences for autoimmune pathology. With this in mind we are studying the selection of B cells in the context of receptor editing using several mouse models. 

 Anergic B cells in humans: immune tolerance or tolerance escape: It has been known for some time that in mouse models autoreactive B cells can enter the mature repertoire but with functional attenuation so that they are unresponsive to binding with our own molecules.  These anergic B cells have long caused a conundrum to immunologists because while being functionally inactivated they maintain their autoreactive specificity.  Importantly, it is known that anergic B cells can be induced by proper stimulation to become fully activated and secrete autoantibodies. For the first time we have now characterized a subset of human B cells that are fully mature but carry autoreactive immunoglobulins.  As in mouse models, these cells are anergic but can be induced to full immune responsiveness ex vivo.  We are now studying the means for the functional inactivation and the role that these anergic human B cells might play in autoimmune diseases such as lupus.

The human B cell response to infectious diseases: The basis of vaccination is often to generate protective titers of blood-borne antibody and memory B cells that can protect against infectious diseases. We have recently devised powerful approaches to rapidly generate monoclonal antibodies that for the first time allow an evaluation of the specificity of ongoing immune responses in humans.  We are working with various collaborators to understand human B cell responses to various infectious diseases of central importance to world health.  In particular we are studying the immune responses to influenza, avian influenza, yellow fever virus, and dengue virus immunization. Our goals are several-fold and include a better understanding of how human B cell responses are mounted, to improve vaccines to these diseases, and finally to generate monoclonal antibodies that could prove to be powerful diagnostic or therapeutic reagents.

SELECTED PAPERS

Brooke, C., Ince, W., Wrammert, J., Ahmed, R., Wilson, P.C., Bennink, J., and Yewdell, J. Most Influenza A Virions Fail to Express At Least One Essential Viral Protein. (2012)  J. Virol. In Press.

Dekosky, B.J., Ippolito, G.C., Deschner, R.P., Lavinder, J.J., Wine, Y., Rawlings, B.M., Varadarajan, N., Giesecke, C., Dörner, T., Andrews, S.F., Wilson, P.C., Hunicke-Smith, S.P., Willson, G., Ellington, A.D., and Georgiou, G. High Throughput Determination of the Antibody VH:VL Paired Repertoire. (2012) Nature Biotech. In Press.

Jiang, N.,  He, J., Weinstein, J.A., Penland, L., Sasaki, S., He, X.S., Dekker, C.L., Zheng, N.Y., Huang, M., Sullivan, M.,Wilson, P.C., Greenberg, H.B., Davis, M.M., Fisher, D.S., and Quake, S.R. High-Throughput Sequencing of the Human Antibody Repertoire in Response to Influenza Vaccination. (2012) Science Trans. Med., In Press.

Andrews, S.F., Zhang, Q., Lim, S., Li, L., Lee, J.H., Zheng, N.Y., Huang, M., Taylor, W.M., Farris, A.D., Ni, D., Meng, W., Luning-Prak, E.T., and Wilson, P.C. Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity. (2012) J. Exp. Med., In Press

Chiu, C., Wrammert, J., Li, G-M., McCausland, M., Wilson, P.C., Ahmed, R. Cross-reactive humoral responses to influenza and their implications for a “universal” vaccine. Annals of the New York Academy of Sciences. (2012) In Press

Smith, K., Muther, J.J., Duke, A.L., McKee, E., Zheng, Y-Z., Wilson, P.C., and James, J.A., Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax®23 are serotype specific and facilitate opsonophagocytosis. (2012) Immunobiology. In Press.

Popova, L., Smith, K., Wilson, P.C., James, J.A., Thompson, L.F., and and G.M. Air. Immunodominance of Antigenic Site B over Site A of Hemagglutinin of Recent H3N2 Influenza Viruses. (2012) PLOS One. In press.


Wilson, P.C., and S. Andrews. Tools to therapeutically harness the human antibody response. (2012) Nature Rev. Immunol. In press.

O'Donnell, C., Vogel, L., Wright, A., Das, S., Wrammert, J., Li, G-M., McCausland, M., Zheng, N.Y., Yewdell, J., Ahmed,R.,Wilson, P.C., and K. Subbarao. Antibody Pressure by a Human Monoclonal Antibody Targeting the 2009 Pandemic H1N1 Virus Hemagglutinin Drives the Emergence of a Virus That is More Virulent in Mice. (2012) mBio. In press.

Li, G-M., Chiu, C., Wrammert, J., McCausland, M., Andrews, S.F., Zheng, N.Y., Lee, J.H., Huang, M., Qu, X., Edupuganti, S., Mulligan, M., Das, S., Yewdell, J., Mehta, A.K., *Wilson, P.C., & *R. Ahmed. Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. (2012) PNAS. Jun 5;109(23):9047-52. 
*Dr. Wilson is the co-corresponding author

Smith K., Crowe S.R., Garman L., Guthridge C.J., Muther J.J., McKee E., Zheng, N.Y., Farris A.D., Guthridge J.M., Wilson P.C., James J.A. Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization. Vaccine. (2012) Jun 13;30(28):4276-83.

Wrammert, J., Onlamoon, N, Akondy, R., S., Perng, G.C., Polsrila, K., Chandele, A., Kwissa, M., Pulendran, B., Wilson, P.C., Wittawatmongkol, O., Yoksan, S., Angkasekwinai, N., Pattanapanyasat, K., Chokephaibulkit, K., and Ahmed, R. Rapid and Massive Virus-Specific Plasmablast Responses during Acute Dengue Virus Infection in Humans. (2012) J. Virology. Mar;86(6):2911-8.

Di Niro, R., Mesin, L., Zheng, N.Y., Morrissey, M., Lee, J. H., Huang, M., Stamnaes, J., Lundin, K.E.A., *Wilson, P.C., and *L.M. Sollid. Abundance in the celiac disease duodenal mucosa of plasma cells secreting transglutaminase 2 specific IgA with low degree of somatic mutation. Nature Med. (2012) Feb 26;18(3):441-5. 
*Dr. Wilson is the co-corresponding author.

Pauli, N., Dunande, C., and Wilson, P.C.  Human Memory B cell responses to infectious diseases. Frontiers in Immunology. (2011) 2011;2(77):1-12.

Sullivan, M., Kaur, Pauli, N., Wilson, P.C., Harnessing the Immune System’s Arsenal: Human Monoclonal Antibody Production for Pandemic Therapeutics and Investigating Immune Responses. The Scientist (F1000 Reports). (2011) 2011;3(17): 1-8.

Terajima, M., Cruz, J., Co, M.D.T., Lee, J.H., Kaur, K., Wrammert, J., Wilson, P.C., and Ennis, F.A., Complement-Dependent Lysis of Influenza A Virus-Infected Cells by Broadly Cross-Reactive Human Monoclonal Antibodies. J. Virology. (2011) Dec;85(24):13463-7.

Kaur, K, Sullivan, Pauli N., Wilson, P.C., Targeting B cells in influenza vaccine design. Trends in Immunology. (2011) Nov;32(11):524-31.

Sasaki, S., Sullivan, M., Narvaez, C. F., Holmes, T., Furman, D., Zheng, N-Y., Nishtala, M., Smith, K., James, J. A., Dekker, C. L., Wrammert, J., Davis, M. M., *Wilson, P. C., *Greenberg, H. B., and *He, X. S. Age-related quantitative and qualitative differences in human B-cell response to inactivated influenza vaccine. (2011) J. Clin. Invest.  Aug 1;121(8):3109-19. 
*Dr. Wilson is a co-corresponding author.

Wrammert J., Koutsonanos, D., Li, G. M., Edupuganti, S., Sui, J., Morrissey, M., McCauslan, M., Skountzou, I., Hornig, M., Lipkin, W. I., Mehta, A., Razavi, B., Del Rio, C., Zheng, N. Y., Lee, J. H., Huang, M., Ali, Z., Kaur, K., Andrews, S. F., Amara, R., Wang, Y., Das, S.R., O’Donnell, C. D., Yewdell, J, W., Subbarao, K., Marasco, W. A., Mulligan, M. J., Compans, R., Ahmed, R., and Wilson, P. C., Human monoclonal antibodies against novel H1N1 influenza virus infection. (2011) J. Exp. Med. 208(1):181-93.

Di Niro, R., Mesin, L., Raki, M., Zheng, N.Y., Lund-Johansen, F., Lundin, K.E.A., Charpilienne, A, Poncet, P, Wilson, P.C., and L.M. Sollid. Rapid generation of rotavirus-specific human monoclonal antibodies from small intestinal mucosa. J. Immunol. (2010) Nov 1;185(9):5377-83.

Mouquet, H., Scheid, J.F., Zoller, M., Ott, R., Shukair, S., Artyomov, M., Pietzsch, J., Connors, M., Pereyra, F., Walker, B., D., Ho, D., Wyatt, R. T., Mascola, J. R., Wilson, P. C., Seaman, M.S., Eisen, H. N., Chakraborty, A. K., Hope, T., Ravetch, J. V., Wardemann, H., and Nussenzweig, M.C., Polyreactivity increases the affinity of anti-HIV antibodies by heteroligation.Nature. (2010) Sep 30;467(7315):591-5.

Andrews, S., and Wilson, P.C., The anergic B cell. Blood. (2010) 115(24):4976-4978.

Smith, K., Garman, L., Wrammert, J., Zheng, N.Y., Capra, J.D., Ahmed, R., and Wilson, P.C. Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nature Protocols. (2009) 4(3):372-84.

Duty, J.A., Szodoray, P., Zheng, N.Y., Koelsch, K.A., Zhang, Q., Mathias, M., Nakken, B., Jared, M., Smith, K., Farris, D.,Wilson, P.C. Functional anergy in a subpopulation of naïve B cells expressing autoreactive receptors in humans. J Exp Med. (2009) Jan 16;206(1):139-51. 

Wrammert, J., Smith, K., Miller, J., Langley, T., Kokko, K., Larsen, C., Zheng, N. Y., Mays, I., Helms, C., James, J., Air, G., Capra, J. D., Ahmed, R., and Wilson, P.C. Rapid cloning of high affinity human monoclonal antibodies against influenza virus. Nature.  (2008) May 29;453(7195):667-71.

Casellas, R., Q. Zhang, N.Y. Zheng, M.D. Mathias, K. Smith, and P.C. Wilson. Ig{kappa} allelic inclusion is a consequence of receptor editing. (2007) J Exp Med 204:153-160.

Koelsch, K., N.Y. Zheng, Q. Zhang, A. Duty, L.A. Abraham, C. Helms, M.D. Mathias, M. Jared, K. Smith, and Wilson, P.C.Mature autoreactive B cells from healthy people permanently class switch to the IgD antibody isotype. J Clin Invest. (2007) Jun;117(6):1558-1565

Crouch,E., Li, Z., Takizawa, M., Fichtner-Feigl, S., Gourzi, P., Montano, C., Feigenbaum, L, Wilson, P., Janz, S., Papavasiliou, F.N., and R. Casellas. Regulation of AID expression in the immune response. J Exp Med. (2007) May 14;204(5):1145-1156

Zheng, N.Y., Wilson, K., Jared, M., and P.C. Wilson.  Intricate targeting of immunoglobulin somatic hypermutation maximizes the efficiency of affinity maturation. J. Exp. Med. (2005) 201(9):1467-1478.

Meffre, E., Schaefer, A., Wardemann, H., Wilson, P., Davis, E., and Nussenzweig, M.C.  Surrogate light chain expressing human peripheral B Cells produce self-reactive antibodies.  J Exp Med. (2004) 199(1):145-150.

Zheng, N.Y., Wilson, K., Wang, X., Boston, A., Kolar, G., Jackson, S.M., Liu, Y.J., Pascual, V., Capra, J.D., and Wilson,P.C.,  Human immunoglobulin selection associated with class-switch and possible tolerogenic origins for C(Delta) class switched B cells. J Clin.Invest (2004) 113:1188-1201.