Somatic mutation in a cultured mouse myeloma cell affects antigen binding.

Area of Science:

• Immunology
• Molecular Biology
• Biochemistry

Background:

• The S107 mouse myeloma cell line produces IgA antibodies specific for phosphocholine.
• This antibody is similar to those produced by BALB/c mice upon immunization.
• Somatic variants with altered antigen-binding capabilities frequently arise in this cell line.

Purpose of the Study:

• To characterize a somatic variant (S107.U1) with altered antigen binding.
• To investigate the molecular basis for changes in antibody affinity.

Main Methods:

• Characterization of the S107.U1 cell line and its antibody.
• Affinity measurements for free hapten and carrier-bound antigen.
• Analysis of amino acid sequences in the variable regions of the immunoglobulin heavy and light chains.

Main Results:

• The S107.U1 variant exhibits reduced binding to phosphocholine when conjugated to a carrier.
• The affinity for free phosphocholine remains unchanged compared to the parent cell line.
• A single amino acid substitution in the JH segment of the heavy chain variable region is identified.

Conclusions:

• A specific amino acid substitution in the JH segment can decrease antibody avidity for a carrier-bound antigen.
• This highlights the critical role of specific residues in the antibody's antigen-binding site.
• Somatic variation provides a model for studying antibody affinity maturation and antigen recognition.