Research

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Michael C. Carroll, Ph.D.

Research Overview

MikeCarroll2The B cell receptor (BCR) is essential for survival of mature B cells and its specificity dictates the cells’ fate from early development through final differentiation into an effector or memory cell.  For example, immature B cells bearing a self-reactive BCR may be eliminated in the bone marrow (check-point I) or spleen (check point II).  Escape at either checkpoint could result in autoimmune disease.   A long-standing interest of the Carroll lab is how B cells encounter antigens, both self- and non-self, and how the local environment influences the outcome.

Antigens are“presented”to B cells in large part by follicular dendritic cells (FDC) via a pathway dependent on complement C3 and receptors CD21 and CD35.  Antigen recognition by antibody or pattern recognition receptors such as the C-type lectins can activate complement resulting in covalent attachment of the third component (C3) to the antigen.  Activated C3 provides a molecular tag that identifies the antigen as foreign.  C3-tagged antigens are transported to FDC via cells bearing complement receptors.  By a mechanism that is not clear, foreign antigens are retained in their native form and made available to cognate B cells over extensive periods.  Whether a similar pathway is involved in “presenting” self-antigen to immature B cells is not known. 

In summary, understanding how foreign antigens are made available to B cells at varying stages in their differentiation would be useful in the design of vaccines and programming of an optimal humoral response to specific pathogens.  Similarly, disrupting B cell access to self-antigen would be desirable in tuning-down the humoral response in autoimmunity.  


About Michael Carroll

Michael Carroll received his Ph.D. in Immunology from the UT Southwestern Medical School (Dallas, TX) under the direction of Dr. J. Donald Capra in 1980; subsequently he trained with Dr. Rodney R. Porter in the Biochemistry Department, Oxford U (Oxford UK). In 1985, he was appointed an Assistant Professor in Pediatrics and the Department of Biological Chemistry at the Children’s Hospital/Harvard Medical School. He was promoted in 1998 to the rank of Professor of Pediatrics, Harvard Medical School and Senior Investigator, The Immune Disease Institute.

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