New regulatory CD19+CD25+ B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids

• A new subset of perforin-producing regulatory B cells enriched at CNS during MS relapse is described.
• To our knowledge, this is the first report demonstrating perforin expression by B cells.
• Our data may add on cell contact mechanisms of immune suppression by BReg during MS relapse.

In multiple sclerosis (MS), the immune damage to the central nervous system results from the net balance between self-reactive and immunoregulatory cells, among other factors. We identified novel perforin-expressing regulatory B-cells (BReg) in patients with clinically isolated syndrome, significantly enriched within the cerebrospinal fluid when compared to peripheral blood, of memory B cell phenotype (CD19+CD25+, CD19+CD25+FoxP3+ and CD19+FoxP3+, p = 0.007, p = 0.06 and p = 0.03, respectively). These BReg subsets were also higher in relapsing–remitting MS during relapse symptoms than in non-clinically active MS patients. Suppressive effects by CD19+CD25+ hi BReg on CD4+ T cell proliferation seem to be mediated at least in part by perforin/granzyme pathway. To our knowledge, this is the first report that shows cytolytic perforin/granzyme granule storage in B cells; the interesting point is its involvement on BReg cell immunosuppressive mechanisms, similarly to that in TReg cells. Our data may extend the understanding of pathophysiological processes in MS immunoregulation.