Natalizumab points at the importance of B cells

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We and to be fair others, suggested the importance of cells within the memory B cell populations many years ago. The important part of hypothesis building is trying to disprove the idea and I would say that over those years the support has built and built. However, still many people do not accept this. As data builds up and up and eventually a light bulb is turned on.

I guess you are bored with this. I’m probably not going to be posting on stuff that I just can’t gush about. Sadly the mirth of the majority has to make way the feelings of a few, who probably don’t read the blog…..so faecal transplants are gone with a flash of gas. I suppose the way to get people to accept ideas, is to develop a treatment and do a clinical trial…..Until that happens I will just have to speculate.

FYI Plasmablasts are cells that can turn into plasma (antibody making) cells. They can be formed from memory B cells

Henriksen et al. Natalizumab differentially affects plasmablasts and B cells in multiple sclerosis Mult scler rel Disord DOI:https://doi.org/10.1016/j.msard.2021.102987

Background: Natalizumab treatment increases the frequencies of B cells in blood but reduces IgG in blood and CSF. Plasmablasts are important in the production of IgG, and the development of plasmablasts is CD49d dependent.

Objective: We hypothesized that natalizumab treatment affects the development of plasmablasts.

Methods: We retrospectively analyzed frequencies and absolute counts of B cell subsets by flow cytometry from a longitudinal cohort of 9 progressive multiple sclerosis (MS) patients treated with natalizumab for 60 weeks, and a cross-sectional relapsing-remitting MS (RRMS) cohort with 17 untreated and 37 treated with natalizumab (17 stable and 20 unstable patients with relapse activity). Additionally, CD49d expression on B cell subsets was examined in 10 healthy controls, and blood and cerebrospinal fluid (CSF) frequencies of B cell subsets were quantified in untreated and natalizumab treated RRMS patients.

Results: In progressive MS, levels of IgG decreased in plasma (p<0.001) from baseline to 60 weeks follow-up. In the progressive MS and RRMS cohorts we observed that natalizumab treatment significantly increased the frequency of B cells (p=0.004; p<0.0001) and several B cell subsets, most pronounced for memory B cell subsets (p=0.0001; p<0.0001), while there was a decrease in plasmablast frequency (p=0.008; p=0.008). In both progressive MS and RRMS the absolute cell counts of B cells increased (p=0.004; p<0.001), which was explained by a significant increase in all subsets, except for plasmablasts. Furthermore, we found decreased memory B cell counts in unstable compared to stable natalizumab-treated patients (p=0.02). The expression of CD49d was higher on plasmablasts compared to other B cell subsets (p<0.0001). In CSF, plasmablasts could not be detected in patients treated with natalizumab, in contrast to an increased frequency in untreated RRMS patients.

Conclusion: We confirm previous studies showing that natalizumab increases circulating number of B cells, particularly memory cells, concomitant with a decrease in plasma IgG concentrations. Moreover, we demonstrate in two separate cohorts that natalizumab treatment markedly decreases frequencies of plasmablasts while the absolute number is stable. Additionally, plasmablasts have high expression of CD49d, and plasmablasts could not be detected in the CSF of natalizumab-treated patients. Finally, memory B cells were found to be reduced in unstable natalizumab-treated patients, which could possibly indicate increased recruitment to the CNS.

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MouseDoctor

2 comments

  • I don’t really understand the technical jargon but I have been on Natalazimab (?) or Tysabri for over 10 years off and on and each time I came off it (we thought I was transitioning to SPMS) I relapsed. This last time I was off for approximately 18 months. I had an MRI to be sure I wasn’t having any activity at about 14 months and all looked good however I felt I was having some disease activity. 3 months later I relapsed, had an MRI and 3 new large lesions had popped up. However Tysabri works, I am 100% confident that it has kept my disease at bay for quite some time! I am now back on Tysabri and starting to feel back to my old self. Thanks for the posts!

  • How does this fit with the biology of natalizumab….”Decreases the frequency of plasma blasts but the absolute number is stable”?

    Also, if natalizumab blocks entry of lymphocytes into the CNS with subsequent increase plasma memory B-cellsthen how does that translate to lower plasmablasts with IgG drop? Is there some negative feedback with memory B cells and plasmablasts?

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