When I was a kid we had a few PC descriptors for non-heterosexual identifying people and now whe have LGBTQIA+ and an every expanding acronym. Yep you as what has this got to do with MS research.
We have anti-CD20 antibodies which are increasingly used and is the major high efficacy class of treatment used in MS and we ask how do they work? The Simple answer is they deplete pathogenic B cells….but no we have to make it more complicated and you can’t talk about anti-CD20 without mentioning CD20+ T cells which either make CD20 or stealit from B cells when the T cells are talking to B cells….so the antibodies are working by depleting the teeny weeny population of T cells causing MS…Now I thinking this like trying to get the ugly sisters hairy foot into Cinderellas slippers…yep it does not make sense….so now we are making it all more confusing with the bisexual lymphocyte who is abit T cell as it has a T cell receptor and abit B cell as it has a B cell receptor notably immunoglobulin M. These cells express CD20 and are depleted with CD20-specific monoclonal antibody….So the type of cell affected by anti-CD20 what happens next….the Questioning B cell…Yep I am only joking but you get the point and I ask why make it complicated when you have an easy answer. So how do we work this out? Does it mean that anti-T cell receptor therapy which should included anti-CD3 will work….If it doesn’t this idea is tosh..However if anti-CD3 therapy works it is then time to say it is because it is working on B cells as when T and B cells talk the B cell nibbles abit of the T cell (This is called trogocytosis). It is important to know as it helps you to know where to go next to make things better.
Paul P, Behzadirad M, Al Hallaf R, Dominguez-Penuela SC, Pardo CA, Jie C, Nourbakhsh B, Hamad ARA. Myelin-Reactive TCR/IgM Dual-Expresser Lymphocytes in Multiple Sclerosis: Linking Pathogenesis to Anti-CD20 Therapy. Immunol Invest. 2025 Sep 17:1-19.
Background: Multiple sclerosis (MS) is an autoimmune disorder driven by myelin autoantigen-specific autoreactive T cells, yet the most effective disease-modifying therapies (DMTs) target B cells. The mechanism underlying this paradox remains unclear. Here, we identify dual-expressor cells (DEs) -a novel lymphocyte population with hybrid T and B cell characteristics, including co-expression of the T cell receptors (TCRαβ) and surface B cell receptors (BCRs), primarily IgM-as potential contributors to MS pathogenesis and inadvertent targets of anti-CD20 DMTs.
Methods: DEs were examined in the peripheral blood and cerebrospinal fluid (CSF) of patients with relapsing-remitting MS (RRMS) compared to healthy controls. Their phenotype and functional properties were characterized, including responses to myelin autoantigens and susceptibility to depletion in a pilot cohort of seven RRMS patients treated with ocrelizumab.
Results: DEs were found at significantly higher frequencies in the peripheral blood of patients with RRMS compared to healthy controls and were further enriched in CSF, where up to 95% expressed CD20, versus ~60% in blood. Furthermore, most of DEs in CSF express CXCR3, indicating involvement of CXCR3-CCL-9, 10 and 11 in their recruiting and maintenance in the CSF of MS patients. Functionally, DEs exhibited robust responses to myelin autoantigens, supporting their relevance in disease. In a pilot cohort of seven RRMS patients, ocrelizumab significantly reduced circulating DE frequencies, confirming their susceptibility to CD20-mediated depletion.
Conclusions: These findings implicate DEs in MS and provide insight into the efficacy of anti-CD20 therapies in a traditionally T cell-driven disease.
Source: multiple-sclerosis-research.org