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B cells in health and disease


B cells are central to the immune system, for instance in their role as antibody producing cells. Antibodies are found on the surface of B cells (BCR) and in blood. Antibodies protect by binding to unique structures on pathogens, which leads to the formation of immune complexes that are disposed off by the body. Each B cell synthesises a unique antibody due to a process in which antibody gene segments are randomly recombined. However, this can also lead to the synthesis of antibodies that recognise self, autoantibodies, one of the hallmarks of autoimmune disease, where immune complexes appear involved in organ damage and destruction. By contrast, immunodeficiency is characterised by a lack of antibodies and is associated with persistent infections. There are also B-lineage cancers, eg acute lymphocytic leukaemia (ALL). These diseases are complex, including gender, genetic and environmental factors.

Our aim is to better understand the molecular and cellular mechanisms underlying the development of disease. We focus on the pre-BCR and BCR, and the importance of these receptors at the checkpoints indicated in the Figure below (red arrows), during B cell development and differentiation in health and disease. Our research translational; our observations in mouse models are translated to healthy individuals and patients, and vice versa.

Checkpoints during B cell development and differentiation.

In the bone marrow, pro-B cells develop into pre-B cells that express a pre-B cell receptor (pre-BCR) on the cell surface. As these cells leave the cell cycle, they develop into immature B (iB) cells that express a BCR, i.e. membrane bound antibody. iB cells leave the bone marrow and migrate via blood to peripheral lymphoid organs, e.g. spleen. Here, as transitional B (TrB) cells, they mature into naïve B cells. As such, they are ready to take part in immune responses provided their BCR bind cognate antigen. In the context of T cells and other immune cells, the B cells are activated and move into structures termed germinal centres. Here, the B cells undergo clonal expansion and the BCRs are diversified in order to increase their affinity for antigen. When the cells leave these structures, they differentiate into memory B cells (MBC) or antibody-secreting plasma cells. Our results suggest that dysfunctional checkpoints are involved in the development of autoimmune diseases and leukaemia.

Research focus: Memory B cells and their role in primary immune-deficiencies, autoimmunity and lymphomas.

  • Grimsholm*, W Ren*, AI Bernardi, H Chen, G Park, A CAmponeschi, D Chen, B Bergmann, N Höök, S Andersson, A Strömberg, I Gjertsson, S Cardell, U Yrlid, A De Riva, and I-L Mårtensson. Absence of surrogate light chain results
in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells. Nature Communications (2015)
  • K Thorarinsdottir*, A Camponeschi*, N Cavallini*, O Grimsholm, L Jacobsson, I Gjertsson* and I-L Mårtensson* (*shared). CD21-/low B cells in human blood are memory cells. Clinical and Experimental Immunology (2016)
  • Marasco, E., Farroni C., Cascioli S., Marcellini V., Scarsella M., Giorda E., Piano Mortari, E., Leonardi, L., Scarselli, A., Valentini, D., Cancrini, C., Duse, M., Grimsholm O., Carsetti R. Activation of B cells with CD40L or CpG measures the functions of different B cell subsets and identifies specific defects in B cells from patients with immunodeficiency. Eur J Immunol. (2016)

 

Professor Lill Mårtensson

Kontaktinformation

Lill Mårtensson-Bopp

Box 480, SE-405 30 Göteborg

Besöksadress:
Guldhedsgatan 10

Telefon:
46 (0)31-342 24 92

Sidansvarig: kommunikation@medicine.gu.se|Sidan uppdaterades: 2017-06-19
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