Education Doube negative memory


In humans B cells can be recognised by the expression of CD19 (a molecule involved in B cell antigen receptor signalling and B cell diferentiation into different B cell sub-types).

Memory B cells are recognised by the presence of a marker called CD27 (as survival factor receptor and activation marker also found on activated T cells) and Immunoglobulin (antibody) arrangements. Antibodies serve are the target recognition molecules for B cells and may be secreted as (IgM, IgA, IgG and sometimes as IgE)

Memory B cells have changed from being a naive/mature B cell (CD19+, CD38+, CD27-) that hasn’t seen its target and express IgD to a memory B cell which has become experienced and loses IgD. This means they will have a more rapid and more robust response to the target next time it is encountered.

Memory B cells express immunoglobulins and these undergo class switching (CSM) after activation, where by the target binding part of the antibody stays the same (except that is undergoes somatic mutation in the hope of creating something even stronger binding (higher affinity) to the target, but the tail of the antibody changed from the proteotype IgD to Ig A, IgG (IgE production probably comes later from IgG memory B cells) and there are IgM class-switched memory B cells. There are also unswitched memory B cells, which express CD27 and IgD (or IgM and IgD). These may not be produced within germinal centres in lymph glands

There is also a memory B cell susbset that has shown rearrangement of its immunoglobulin (IgG/IgA) molecules indicating activation but does not expressed either IgD or CD27 (so called double negative memory (DNM) B cells. They tend to have less mutation than CSM cells indicating that they are not CSM (CD27+, IgD-) that have lost CD27-

In the paper below they look at the DNM B cells and conclude that there are more of them in some people with MS. They sequenced the antibody molecules to determine their gene structures. Althoug there are some CSM and DNM with similar immunolglobulin sequences many or different. The question is what are they doing in MS?. The answer is I don’t know. This paper doesn’t tell us either. But there are there for a reason.

Why do these posts? Well…I don’t know anything about double negative memory B cells and I am trying to learn about memory B cells. Why? Because they may be important based on response to therapy. Why not spend my time on T cells?, I know more on T cells and there are plenty of reviews on the T cell.

So we may as well learn together, so when I start talking about them in super scientific posts in the future, on the off-chance that they become important, then you know what they are.

Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgDCD27 Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients.Fraussen J, Marquez S, Takata K, Beckers L, Montes Diaz G, Zografou C, Van Wijmeersch B, Villar LM, O’Connor KC, Kleinstein SH, Somers V. J Immunol. 2019 Aug 7. pii: ji1801236. doi: 10.4049/jimmunol.1801236. [Epub ahead of print]

IgDCD27 double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis(MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgDCD27+ class-switched memory (CSM) and IgD+CD27 naive B cells of HC (n = 48) and MS patients (n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients (n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.

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  • Talking of immunoglobulins…..
    Do low IGm levels have anything to do with MS?

    Is having low levels good in terms of the immune system not being triggered, thereby not causing more lesions?

  • Thanks for the effort to educate us. Can you comment more about the main differences between memory B cells and plasma cells? Cheers.

    • Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen (foreign substance), where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell.

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