Highly related immunoglobulin light chain sequences in different multiple sclerosis patients

Area of Science:

• Immunology
• Neuroscience
• Genetics

Background:

• Oligoclonal immunoglobulin G and free light chains in CSF are common in multiple sclerosis (MS).
• The presence of homologous cerebrospinal fluid (CSF) light chain sequences among different MS patients was previously unknown.
• A specific kappa light chain variable region (V) probe hybridized to CSF B cells in many MS patients but few controls.

Purpose of the Study:

• To investigate sequence homology of kappa light chains in CSF B cells from different individuals with MS.
• To determine if shared kappa light chain sequences in MS CSF B cells relate to antibodies against myelin basic protein (MBP).

Main Methods:

• Utilized Southern blotting to analyze kappa light chain variable region (V) sequences from CSF B cells.
• Compared Vkappa cDNA sequences from MS patients with those from controls and mouse anti-myelin basic protein (MBP) antibodies.

Main Results:

• Identified remarkable sequence similarity in certain Vkappa from CSF B cells across different MS patients.
• Observed high sequence homology, including complementarity determining regions (CDRs), among MS patient light chains.
• Found marked sequence homology between MS patient light chains and mouse antibodies against myelin basic protein (MBP).

Conclusions:

• The same or very similar kappa light chain variable regions can be shared by CSF B lymphocytes from different individuals with MS.
• These findings suggest a potential role for shared B cell receptor specificities in MS pathogenesis.
• The homology with anti-myelin basic protein (MBP) antibodies supports the hypothesis of an autoimmune response targeting MBP in MS.