Activated B Cells Participating in the Anti-Myelin Response Are Excluded from the Inflamed Central Nervous System in a Model of Autoimmunity that Allows for B Cell Recognition of Autoantigen

Abstract

Once activated, T cells gain the ability to access both healthy and inflamed nonlymphoid tissues. They are then reactivated to remain in the tissue and exert their effector function only if they encounter their specific Ag. In this study, we set out to determine if the same is true for B cells using a mouse model of CNS autoimmunity that incorporates both T and B cell recognition of a myelin autoantigen. Both T and B cells were common infiltrates of spinal cords in diseased mice. However, unlike T cells, anti-myelin B cells were excluded from the inflamed tissue. Further, CNS B cells did not have a phenotype consistent with Ag-specific activation as it occurs in lymphatic tissue. Instead, they expressed elevated levels of CD80, indicating that B cells may contribute to local inflammation through nonantigen-specific mechanisms.

Autoreactive T cells preferentially drive differentiation of non-responsive memory B cells at the expense of germinal center maintenance

“…Further, subcutaneous immunization with MOG protein is a well-established method to induce the anti-myelin autoimmune model experimental autoimmune encephalomyelitis (EAE). In our hands, mice immunized with mMOG tag develop a robust disease with evidence that GC-derived anti-MOG B cells contribute to both disease severity and chronic disease course (Dang et al, 2015; Tesfagiorgis et al, 2017). Therefore, although short-lived, the MOG GC is productive.…”

B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis

“…Exclusion of B cells from the CNS results in reduced severity of EAE induced by rhMOG yet exacerbates EAE induced by MOG 35-55 peptide, indicating that access to the CNS is required for EAE mediated by B cell antigen presentation yet can also be important for regulatory B cells to ameliorate disease [ 49 – 51 ]. In contrast, Tesfagiorgis et al found that antigen-nonspecific B cells are recruited to the CNS compartment while myelin-specific B cells remain in the peripheral draining lymph nodes in a model of active EAE that requires B cells [ 52 ]. In our model, the relative infrequency of B cells observed in the CNS of mice that develop EAE may reflect the ease with which MOG-specific B cells capture their soluble protein antigens to present to T cells within the CNS compartment.…”

Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity

“…The blood, lymph nodes (inguinal, axillary, and cervical), spleen and the spinal cord were harvested from mice for flow cytometry analysis as previously described (18, 33). Briefly, blood was isolated through a cardiac puncture with needles pre-washed with 0.5M EDTA, after which the mouse was perfused with ice cold PBS prior to harvesting other tissues.…”

“…The blood, lymph nodes (inguinal, axillary, and cervical), spleen and the spinal cord were harvested from mice for flow cytometry analysis as previously described (18,33…”

“…Indeed, EAE induced in mice by immunization with human myelin oligodendrocyte glycoprotein (MOG) is completely dependent on B cells through the production of anti-MOG antibodies (31). Nevertheless, we have shown that the B cell anti-myelin response is short-lived (32) and that anti-myelin B cells are not found in meningeal clusters in the inflamed spinal cord in either sEAE or MOG-protein induced EAE (33). Therefore, the role of anti-myelin-specific B cells may be confined to the initiation of the disease, and thus the contribution of B cells to the chronic phase of disease is likely from some other, non-myelin specific population and may include those that accumulate in the CNS.…”