B-less: a strain of profoundly B cell-deficient mice expressing a human lambda transgene

Area of Science:

• Immunology
• Genetics
• Transgenic Models

Background:

• Transgenic mouse models are crucial for studying gene function and immune system development.
• Understanding B cell development is key to immune system health and disease.

Purpose of the Study:

• To investigate the effects of human lambda light chain gene expression in transgenic mice.
• To characterize the B cell deficiency and infection susceptibility observed in the 'B-less' mouse strain.

Main Methods:

• Creation of transgenic mouse strains with human lambda light chain gene and mouse immunoglobulin heavy chain enhancer.
• Analysis of transgene expression in various tissues.
• Phenotypic analysis including B cell counts, immunoglobulin levels, and susceptibility to infections.
• Cell culture and bone marrow graft chimeras to assess cell-autonomous defects.
• Flow cytometry and mitogen stimulation assays to evaluate T cell lineage.

Main Results:

• Transgene expression was high in immune organs like bone marrow, thymus, spleen, and lymph nodes.
• The 'B-less' transgenic line exhibited profound deficiency in immature and mature B cells and circulating immunoglobulins.
• B cell defects were cell-autonomous.
• T cell lineage remained largely normal.
• The B cell deficiency phenotype is likely due to dominant transgene expression, not insertional mutagenesis.
• Genetic background significantly impacts phenotype suppression, with C57BL/6 genome containing suppressors.

Conclusions:

• Expression of the human lambda light chain transgene can lead to a dominant B cell deficiency.
• The 'B-less' phenotype highlights the critical role of B cells in combating bacterial and viral infections.
• Genetic background plays a significant role in modulating the effects of transgenes on immune cell development.