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Updated: May 12, 2026

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo
A J Ligocki1, W H Rounds, E M Cameron
1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Abstract:
Patients with the autoimmune disease multiple sclerosis (MS) typically present with the clinically isolated syndromes (CIS) transverse myelitis (TM) or optic neuritis (ON). B-cell disturbances have been well documented in patients with MS and CIS patients with ON, but not in CIS patients with TM, despite the fact that these patients have the worst clinical outcome of all CIS types. The goal of this study was to characterize the B-cell populations and immunoglobulin genetics in TM patients. We found a unique expansion of CD27(high) plasmablasts in both the cerebrospinal fluid and periphery of TM patients that is not present in ON patients. Additionally, plasmablasts from TM patients show evidence for positive selection with increased somatic hypermutation accumulation in VH4(+) B cells and receptor editing that is not observed in ON patients. These characteristics unique to TM patients may impact disease severity and progression.
Insights
Transverse myelitis (TM) patients show unique B-cell changes, including expanded plasmablasts and altered immunoglobulin genetics, not seen in optic neuritis (ON) patients. These findings may explain TM
Area of Science:
- Immunology
- Neuroimmunology
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) and clinically isolated syndromes (CIS) involve B-cell disturbances.
- Transverse myelitis (TM) and optic neuritis (ON) are common CIS presentations.
- TM patients exhibit worse clinical outcomes, yet their B-cell profiles remain understudied.
Purpose of the Study:
- To investigate B-cell populations and immunoglobulin genetics in CIS patients with TM.
- To compare B-cell characteristics between TM and ON patients.
Main Methods:
- Analysis of cerebrospinal fluid and peripheral blood B-cell populations.
- Characterization of CD27(high) plasmablasts.
- Assessment of immunoglobulin gene somatic hypermutation and receptor editing in VH4(+) B cells.
Main Results:
- TM patients displayed a unique expansion of CD27(high) plasmablasts in both CSF and periphery, absent in ON patients.
- TM patient plasmablasts showed evidence of positive selection and increased somatic hypermutation in VH4(+) B cells.
- Receptor editing was observed in TM patient B cells, but not in ON patients.
Conclusions:
- CIS patients with TM have distinct B-cell abnormalities compared to ON patients.
- These unique B-cell characteristics in TM may contribute to disease severity and progression.
- Further research into these B-cell differences could inform targeted therapies for MS and CIS.
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