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Surrogate light chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by marginal zone B cells

Artikel i vetenskaplig tidskrift
Författare Weicheng Ren
Ola Grimsholm
Angelina I Bernardi
Nina Höök
Anna Stern
Nicola Cavallini
Inga-Lill Mårtensson
Publicerad i European Journal of Immunology
Volym 45
Nummer/häfte 4
Sidor 1228-1237
ISSN 0014-2980
Publiceringsår 2015
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Sidor 1228-1237
Språk en
Länkar dx.doi.org/10.1002/eji.201444917
Ämnesord Autoantibodies , Autoimmunity , Light chain recombination , Marginal zone B cells , Pre-BCR
Ämneskategorier Immunbiologi

Sammanfattning

Selection of the primary antibody repertoire takes place in pro-/pre-B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B-cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody-producing cells is due to an inability of the resultant B-cell receptors to induce central and/or peripheral B-cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B-cell pool. Those that enter the marginal zone (MZ) B-cell pool escape selection and survive, possibly due to the B-lymphopenia and elevated levels of B-cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti-dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B-cell tolerance and inhibits anti-DNA antibody production by MZ B cells.

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