Birgitta Heyman research group

Antibody feedback regulation

Antibodies in complex with their specific antigen can feedback-regulate antibody responses against this antigen. Depending on antibody class, affinity and type of antigen, complete suppression or 10-1000-fold enhancement of the in vivo immune response can be seen. Both passively administered and actively produced antibodies are effective, suggesting a biological role. One of the most successful clinical applications of modern immunology is Rhesus prophylaxis, where administration of suppressive IgG anti-RhD prevents Rh-immunization in Rh negative mothers carrying Rh postive fetuses. This antibody treatment has almost eradicated hemolytic disease of the newborn in industrialized countries. In spite of this successful treatment, the mechanisms behind feedback regulation are poorly understood.

An immune complex is composed of antigen/antibody/complement (if the antibody is able to activate complement). Such immune complexes can bind to the B-cell receptor, Fc-receptors (FcR) and complement receptors (CR). Ligation and co-ligation of these receptors on the B cell surface can negatively or positively regulate the B cell. Increased uptake of complexed antigen by antigen-presenting cells via FcRs or CRs can enhance T helper cell activation. Follicular dendritic cells (FDC) do not express MHC-II molecules and do not present antigen to T cells. They are interspersed in the B cell follicles of the spleen and lymph nodes and interact closely with B cells. Since FDC express both FcR and CR, they may capture immune complexes and act as a concentration device, facilitating antigen recognition by the B cells. A novel interesting function of antibodies is to transport antigen into the optimal locations in secondary lymphoid organs.

The main objective of our research is to clarify the mechanisms behind antibody feedback regulation, both during a normal immune response and in autoimmune diseases and allergies.