CD98 is a potential target for ablating B cell clonal expansion and autoantibody in multiple sclerosis

- CD98 is required on B cells for efficient induction of MOG-induced EAE.
- Loss of B cell CD98 blocks autoantibody production after immunization with MOG.
- Targeting CD98 does not appear to affect steady-state B cell functions.
- CD98 is a potential therapeutic target in the antibody-dependent subset of MS.

Current B cell-directed therapies for multiple sclerosis impact multiple B cell functions. CD98hc enables B cell clonal expansion and antibody production. I probed the relative importance of autoantibody secretion vs. other B cell functions in MS and targeted CD98hc as a possible therapeutic strategy. I report that the loss of CD98hc function in B cells largely prevents autoantibody production while preserving antigen-presenting and T cell-directing capacities. Mice lacking CD98hc in B cells are protected from EAE; importantly this is overcome with autoantibody-containing plasma. Thus CD98hc blockade is a possible avenue to treat MS by inhibiting clonal expansion and autoantibody.