Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis

Abstract

Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis and IND patients, but were largely absent in NIND patients. In the CSF, the majority of B cells had a phenotype of memory B cells and short-lived plasma blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients.

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].…”

Screening Random Peptide Libraries with Subacute Sclerosing PanencephalitisBrain-Derived Recombinant Antibodies Identifies Multiple Epitopes in the C-Terminal Region of the Measles Virus Nucleocapsid Protein

“…Because both rAbs 2B4 and 3B recognize different linear protein epitopes within the MV N protein, the utility of rAbs recognizing discontinuous epitopes for identification of unknown antigens is still uncertain. The screening of libraries containing longer peptide sequences or that are constrained by cysteine residues may aid in the identification of more-complex, discontinuous epitopes (4,9). It is possible that many of the rAbs derived from MS and other inflammatory disease CSF samples will recognize discontinuous epitopes and perhaps even carbohydrates.…”

“…In CNS infectious diseases, such as subacute sclerosing panencephalitis (SSPE), neurosyphilis, mumps meningitis, progressive rubella panencephalitis, cryptococcal meningitis, and varicella zoster virus vasculitis, the oligoclonal IgG is directed largely against the infectious agent that causes the disease (reviewed in reference 12). Increased CNS IgG synthesis is accompanied by an elevated number of CD19 ϩ B cells and the appearance of post-germinal center reaction plasmablast/plasma cells (4,6,18). We previously used laser capture microdissection and single-cell PCR to identify expanded clones among the CD38 ϩ B cells found within the parenchyma of SSPE brain (3).…”

Illuminating vitamin D effects on B-cells - the multiple sclerosis perspective

“…Since these IgG levels in vivo are not influenced by vitamin D, vitamin D does not seem to influence long-lived plasma cell generation in germinal centres. With respect to intrathecal IgG levels, which are predominantly produced by short-lived plasma blasts, 23 one would expect also a decrease upon vitamin D supplementation. We speculate that germinal centre processes in ELFs are inadequate for the generation of long-lived plasma cells and, therefore, that IgG production initiated within these ELFs is susceptible to inhibition by vitamin D (Fig.…”

“…In fact, the majority of these B cells consist of CD19 + CD27 + CD 138 À memory B cells. 23,24 Furthermore, besides being present in the CSF, B cells, plasma blasts, plasma cells and antibodies have been found in the brain parenchyma, white matter lesions and leptomeninges of patients with MS. Because these CSF/CNS B cells largely are antigenexperienced B cells, it has been questioned whether the activation and maturation of these cells occur within or outside the CNS, or perhaps even on both sides of the blood-brain barrier. Clonally related B cells in MS have been found both in the CNS and the peripheral blood compartment, implying that they are able to exchange across the blood-brain barrier.…”