Michael C. Carroll
Department of Pediatrics (Pathology), Senior Investigator/Professor
Director, Graduate Program in Immunology
200 Longwood Ave.
WAB, Room 251
Boston, MA 02115
Tel: 617-713-8700
Fax: 617-713-8702
Email: michael.carroll@childrens.harvard.edu
Lab Members: 4 postdoctoral fellows, 2 graduate students
Visit my lab page here.
The 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.
References:
Trafficking of B Cell Antigen in Lymph Nodes
Gonzalez SF, Degn SE, Pitcher LA, Woodruff MC, Heesters BA, Carroll MC.
Annual Reviews of Immunology (2011), Volume: 23, Issue: 29, Pages: 215-233
Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes
Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Kim YA, Cloninger MJ, Martinez-Pomares L, Gordon S, Turley SJ, and Carroll MC.
Nature Immunology (2010), Volume: 11, Issue: 5, Pages: 427-434
Conduits Mediate Transport of Low-Molecular-Weight Antigen to Lymph Node Follicles
Roozendaal, R.; Mempel, T. R.; Pitcher, L. A.; Gonzalez, S. F.; Verschoor, A.; Mebius, R. E.; von Andrian, U. H.; Carroll, M. C.
Journal of Immunology (2009), Volume: 30, Issue: 2, Pages: 264-276
Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice
Issac M. Chiu, Hemali Phatnani, Michael Kuligowski, Juan C. Tapia, Monica A. Carrasco, Ming Zhang, Tom Maniatis, and Michael C. Carroll.
PNAS (12/8/2009), Volume: 106, Issue: 49, Pages: 20960 - 20965
For a complete listing of publications click here.
Last Update: 1/3/2013