B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation

Abstract

B cells have long played an enigmatic role in the scenario of multiple sclerosis pathogenesis. This review summarizes recent progress in our understanding of B-cell trafficking, survival, and differentiation in the central nervous system (CNS). We propose four possible routes of intrathecal immunoglobulin-producing cells. The inflammatory CNS provides a unique, B-cell-friendly environment, in which B lineage cells, notably long-lived plasma cells, can survive for many years, perhaps even for a lifetime. These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands. Furthermore, we highlight similarities and differences of intrathecal immunoglobulin production in multiple sclerosis patients and patients with other CNS inflammatory conditions. Finally, we outline the possibly double-edged effects of B cells and immunoglobulin in the CNS and discuss various therapeutic strategies for targeting the B-cell response.

Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis

“…As described above, the reactivity to HSP in RRMS appears related to the more inflammatory nature of MS in the initial relapsing stages. We believe that the different antibody signatures against CNS antigens also reflect the ongoing inflammatory process in the brain due to the traffic of immune cells, antibodies and/or antigen between the brain and periphery (36,43). This is supported by our finding of unique serum patterns linked to type I or type II pathology as measured by brain biopsy.…”

“…Although cell-mediated immunity against myelin antigens is felt to play a major role in MS (1), B cells and autoantibodies also appear to contribute to disease pathogenesis (36). How do our results relate to the role antibodies vs. T cells in the MS disease process?…”

Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin‐specific antibodies

“…Furthermore, the CD138 + cell population in the CSF includes CD138 + /CD19 + plasma blasts, which have been suggested to be an important B cell effector subset in MS [17]. A growing body of evidence attributes the CNS with the capability to provide an environment supporting B cell development [18,19]. However, little is currently known about the immunopathological relevance of focused B cell responses within the CNS compartment in MS, and the target antigens or tissues of antibodies produced by cePC remain to be determined.…”

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

“…In APCs antigen-antibody complexes can remain intact after internalisation and fragmentation by proteases along the antigen-processing pathway, thus protecting residues from proteolysis and thereby modulate the presentation of peptides to T cells (Quaratino 2005). Consequently, the fine specificity of a soluble antibody that binds to an antigen can affect the processing and presentation of T cell epitopes by either boosting or (Meinl 2006). It would be interesting to examine the persistence of intrathecal virus-specific oligoclonal IgG antibodies after anti-CD20 B cell depletion to further understand the role of both these B cell subsets and virus-specific antibodies in MS pathogenesis.…”