22 Oct 2026
Edgar Meinl and an international team have discovered that B cells and T cells acquire surface markers from each other upon co-activation, challenging the traditional way to distinguish these immune cell types.
© Selia Baier et al.
The researchers call these cells “masquerading lymphocytes” and provide evidence that they contribute to the immunopathogenesis of multiple sclerosis (MS).
T cells and B cells are key components of the adaptive immune system. They are usually distinguished by specific surface proteins, such as CD3 on T cells and CD20 on B cells. This conceptual division has shaped our understanding of adaptive immunity and provides the basis for the use of targeted therapies in autoimmune diseases such as multiple sclerosis.
However, recent studies have found that around 1 to 5 % of T cells in human blood display CD20, albeit at lower levels than B cells. This was observed in patients with MS, other immunopathologies, healthy controls and in the context of immunodeficiency viruses. To investigate this phenomenon, the researchers around Edgar Meinl analyzed CD3+CD20+ cells by combining single-cell proteogenomics, fluorescence-activated cell sorting (FACS) and imaging flow cytometry.
Their analyses identified CD3+ B cells and found that about 40 % of plasmablasts displayed CD3 in both blood and tonsils. In tonsils, where T-B interactions occur, about 80 % of follicular helper T (Tfh) cells displayed CD20.
This study showed that coactivation of T-cells and B cells with direct cell contact induced an exchange of surface markers through a process known as trogocytosis, in which cells acquire membrane components from other cells through direct contact. The researchers call the resulting cells “masquerading lymphocytes” and visualized them by imaging flow cytometry.
A potential role in multiple sclerosis
The team found that CD20+ T cells were markedly enriched in the cerebrospinal fluid of people with MS. These cells showed gene expression patterns associated with cytotoxic activity, accumulated in areas of inflammation around blood vessels in the brain of MS patients and displayed increased reactivity to myelin antigens. Myelin is the insulating layer surrounding nerve fibers and a key target of the immune response in MS.
The researchers also investigated ofatumumab, an antibody to CD20 used to treat MS. This treatment depleted masquerading lymphocytes and prevented their reinduction, suggesting that it affects these cells beyond conventional B cell targeting.
Rethinking immune cell identity
Together, this study identifies CD3+ B cells as footprints of T-B interactions thereby shifting the paradigm of lymphocyte-specific surface markers and implicates masquerading lymphocytes as active contributors to MS immunopathology.
Publication: Selia Baier et al.: T-B interactions yield CD3+ B cells and CD20+ T cells with pathogenic features in multiple sclerosis. Proc Natl Acad Sci U S A, October 2026