Friday, 21 November 2014

B cell presentation of myelin

Brimnes MK, Hansen BE, Nielsen LK, Dziegiel MH, Nielsen CH.
Uptake and Presentation of Myelin Basic Protein by Normal Human B Cells. PLoS One. 2014; 9(11):e113388.

B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35) and CR2 (CD21) both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.


How do the anti-CD20 antibodies work? Is this via killing EBV-infected  cells or is it because B cells present antigens to T cells and by depleting these T cells get less stimulation.  We know that HLA-DR15 is one of the major risk factors for MS susceptibility. Some people think that myelin basic protein is a potential target in MS. I think one of the reasons why this CNS and peripheral nervous system antigen is well researched is because it is abundant but is water soluble and easy to purify unlike the better candidates which are not as abundant in the peripheral nerves. In this study they found that few B cells presented MBP in the absence of blood proteins, but when the MBP was mixed with blood, the complement proteins can bind to it. The complement system is part of the immune system that is part of a system designed to get rid of pathogens that cause disease. It is a enzymatic cascade where one  protein is activated it then activates the next component and so on. One job is to punch holes into infected bacteria or infected cells to kill them another function is to coat the bacteria so it is attractive to be eaten by phagocytic (engulfing) cells, some of which are antigen presenting cells by a process called opsinisation, using complement receptors. In this study these B cells expressed a marker CD27. This is the subset of B cells that Lemtrada depletes, another subset of B cells expand quickly after Lemtrada.  These B cells expressed CD86 (B7-2) which is a protein that binds to CD28 on T cells and is required to be stimulated in addition to the T cell receptor that sees the antigen and the MHC for it to be activated. In this study they stimulated T cells that make interleukin 10 a T cell regulatory factor and an inference that presentation in the blood may dampen down the immune response. IL-10 is also a B cell stimulatory factor socouldit be a bad thing? On balance removing B cells is a good thing

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