Plasmablasts are a highly differentiated, antibody secreting B cell subset whose prevalence correlates with disease activity in Multiple Sclerosis (MS). For most patients experiencing partial transverse myelitis (PTM= inflammation of the spinal cord), plasmablasts are elevated in the blood at the first clinical presentation of disease (known as a clinically isolated syndrome or CIS). In this study we found that many of these peripheral plasmablasts are autoreactive and recognize primarily gray matter targets in brain tissue. These plasmablasts express antibodies that over-utilize immunoglobulin heavy chain V-region subgroup 4 (VH4) genes, and the highly mutated VH4+ plasmablast antibodies recognize intracellular antigens of neurons and astrocytes. Most of the autoreactive, highly mutated VH4+ plasmablast antibodies recognize only a portion of cortical neurons, indicating that the response may be specific to neuronal subgroups or layers. Furthermore, CIS-PTM patients with this plasmablast response also exhibit modest reactivity toward neuroantigens in the plasma IgG antibody pool. Taken together, these data indicate that expanded VH4+ peripheral plasmablasts in early MS patients recognize brain gray matter antigens. Peripheral plasmablasts may be participating in the autoimmune response associated with MS, and provide an interesting avenue for investigating the expansion of autoreactive B cells at the time of the first documented clinical event.
Rivas JR, Ireland SJ, Chkheidze R, Rounds WH, Lim J, Johnson J, Ramirez DM, Ligocki AJ, Chen D, Guzman AA, Woodhall M, Wilson PC, Meffre E, White C , Greenberg BM, Waters P, Cowell LG, Stowe AM, Monson NL. Peripheral VH4+ plasmablasts demonstrate autoreactive B cell expansion toward brain antigens in early multiple sclerosis patients. Acta Neuropathol. 2016 [Epub ahead of print]
Is MS a T or a B cell condition?
However it is absolutely the case that there is antibody mediated autoimmunity in MS and it is increasingly clear that the dominant responses are not against myelin…so so much for myelin basic protein? They react with nerve and grey matter proteins. The question we ask is the antibody a primary target or a secondary issue where by damage liberates cell contents and trigger antibody response and a reason why they are present in the blood. We need to be able to be follow the generation of antibody responses.