Claes N, Fraussen J, Vanheusden M, Hellings N, Stinissen P, Van Wijmeersch B, Hupperts R, Somers V.Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients. J Immunol. 2016 Nov 11. pii: 1502448. [Epub ahead of print]
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD-CD27- (double negative, DN) and CD21-CD11c+(CD21low) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21low B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21low (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients. The majority of DN B cells had an IgG+ memory phenotype, whereas CD21low B cells consisted of a mixed population of CD27- naive, CD27+ memory, IgG+, and IgM+ cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class-switched memory B cells and intermediate costimulatory molecule expression between naive and class-switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21low B cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age-associated B cells. DN and CD21low B cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines
What does this all mean, well not much I think as the changes only occur at best in about 25% of pwMS, but I think 2017 is going to be the year of the B cell as ocrelizumab hopefully gets a licence for treatment of MS, either that or rituximab use develops.
What are B cells?
These are the cells that produce antibodies and are made in the bone marrow. There are loads of diferent types of B cell, which can be recognised by their surface marker expressssion. The cell that produces MS are called plasma cells. These are made in germinal centres (GC) in lymph glands
So in the germinal centres you find the plasma cells, they come from cells that develop from the stem cell and express markers along the way. The mature cells are also known as naive cells and can be recognised by the expression of lack of expression of certain markers like CD21 and CD27
The markers are varied depending on the stage of development
Anti CD20 is what ocrelizumab and rituximab hits