B and T lymphocytes are unique in that they actively change their genetic material during differentiation. Early development is characterized by random combination of gene segments (V(D)J recombination) to create diversity. Later, when B cells are activated, their antibody genes are further diversified through two other processes, class switch recombination that change antibody class from IgM to other classes, and somatic hypermutation that creates diversity from which cells with high affinity binding antibodies are subsequently selected. These two processes mainly occur in specialized structures, germinal centres, that form in peripheral organs during immune responses.
Our main research interest is peripheral B lymphocyte activation, the germinal centre reaction and the two processes that are involved in changing antibody genes during activation. Full activation of B cells requires at least two signals. First membrane-bound antibodies need to bind antigen, then the cells must receive further activation signals from other cells. The most well known such second signal is an interaction between CD40 on the B cell with CD40L on an activated T cell that is crucial for germinal centre reactions. Recently, other signals that can induce class switch recombination in the absence of germinal centres have however been identified. These include endogenous factors such as BAFF and APRIL produced by myeloid cells, and microbial products detected through binding to toll like receptors.
Currently, we are studying differences in intracellular B lymphocyte signals after stimulation with various second signals, secreted factors important for germinal centre B cells and lymphomas, and DNA repair enzymes involved in mutagenesis of antibody genes. In addition, we are studying the development of the B cell compartment in bone marrow transplanted children, and germinal centre dependent and independent pathways for IgA antibody production in the gut.
Bemark M, Neuberger MS. (2003). By-products of immunoglobulin somatic hypermutation. Genes Chromosomes Cancer. 38: 32-39
Zander L, Bemark M. (2004). Immortalized mouse cell lines with an inactivated Rev3 gene are hypersensitive to UV irradiation and cisplatin treatment. DNA repair 3: 743-752.
Shen X, Jun S, O´Neal LE, Sonoda E, Bemark M, Sale JE, Li L. (2006). REV3 and REV1 play major roles in recombination-independent repair of DNA interstrand cross-links mediated by monoubiquitinated PCNA. J Biol Chem 281: 13869-13872.
Bergkvist P, Stensson A, Bemark M, Lycke N. (2006). IgA B cell differentiation in the absence of CD40 cognate interactions is independent of germinal centres and does not occur in gut lamina propria J Immunol. In press.