B-cell Ontogeny and the Humoral Immune Response
1. Development of the immune system: Hemopoietic stem cells, hemopoiesis in the embrio and in the adult, transcription factors and their role in lineage decision and B cell commitment
2. Antigen independent B cell development in the bone marrow: Pro-B, pre-B, and immature B cells - phenotypic and functional differences, the B cell receptor driven positive and negative selection, cytokine- and chemokine-dependent regulation of the development, receptor editing
3. The immunoglobulin gene rearrangement. Germline configuration of H and L chain loci, recombination signal sequences, the function of Rag1/Rag2, the 23/12 rule, rearrangement of the H chain and of the L chain, the protein complex regulating the recombination, levels of the development of variability, class switch recombination, the role of the activation induced citidine deaminase (AID)
4. B cell development in the periphery: Transitional B cells, marginal zone B cells, follicular B cells, maturation and survival regulated by B cell activating factor (BAFF), encountering the antigen, germinal centrum formation, receptor revision
5. Antigen dependent B cell development: Developmental checkpoints in the germinal centers, positive and negative selection, The role of follicular dendritic cells. Somatic mutation, affinity maturation, isotype switch, development of antibody repertoire
6. The B cell receptor complex (BCR), and B cell signaling: Composition of BCR, localization of BCR in membrane rafts, membrane proximal signals mediated by BCR cross--kinase mediated pathway, the MAPK pathway, transcription factors activation. Co-receptors in B cell signaling
7. T cell dependent an T cell independent B cell responses Characterization of T cell independent 1, T cell independent 2 antigens, signals mediated by T lymphocyte derived cytokines. Two signals are necessary for B cell activation. The role of T independent response in bacterial infection
8. Immunological memory and the secondary immune response Development of memory B cells and long life plasma cells, survival and maintenance of the memory compartment. Models of homeostasis in the memory pool. Memory and autoimmunity. Antibody production during the secondary immune response. Vaccination and the immunological memory.
9. Development and role of B 1 cells Non-conventional B cells, CD5+ and CD5- B1 cells, comparison of the development of B 1 and B2 cells, antigens recognized by B1 cells, antibodies produced by B1 cells, B1 cells and autoimmunity
10. Mucosal immune response: MALT, GALT. The role of IgA.
11. Regulation of the humoral immune response Positive and negative signaling in B cells, regulation by Immunoreceptor Tyrosin based Inhibitory Motif (ITIM) containing receptors, regulation of the humoral immune response by cytokines.
12. Effector mechanisms of B cell response Function of the immunoglobulin isotypes, neutralization of pathogens, activation of the complement system, opsonized phagocytosis mediated by Fc and complement receptors, antibody mediated cellular cytotoxicity – a practical application in Rh+ incompatibility, immune complex mediated cytokine release, inflammation, delayed type hypersensitivity.
Selected reviews from Current Opinion in Immunology and Nature Reviews in Immunology