Michael C. Carroll
Program Head, Graduate Program in Immunology
200 Longwood Ave.
WAB, Room 251
Boston, MA 02115
Tel: 617-713-8700
Fax: 617-713-8715
Email: michael.carroll@childrens.harvard.edu
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 (see Figure 1). 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:
Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction. Haas M, Alicot EM, Scheurpf F, Chiu I, Li J, Moore FD Jr, Carroll MC. Cardiovascular Research (2010), Volume: 87, Issue: 4, Pages: 617-627
Complement-dependent transport of antigen into B cell follicles. Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Turley SJ, Carroll MC. Journal of Immunology (2010), Volume: 185, Issue: 5, Pages: 2659-2664
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
The role of innate immunity in B cell acquisition of antigen within LNs Gonzalez SF, Kuligowski MP, Pitcher LA, Roozendaal R, Carroll MC. Advances in Immunology (2010), Volume: 106, Pages: 1-19
Trafficking of B cell antigen in lymph nodes. Gonzalez SF, Degn SE, Pitcher LA, Woodruff M, Heesters BA, Carroll MC. Annu Rev Immunol. 2011 Apr 23;29:215-33.
Last Update: 12/13/2012