Class switching mechanism in antibodies : A conformational and structural investigation of the B-cell repertoire diversity of the CDR3

Abstract: A process called class switching recombination (CSR) regulates the production of isotypes by enabling the switch of producing unspecific IgM or IgD to producing IgG, IgE, or IgA by causing an irreversible genomic rearrangement. Recent studies indicate a gap in the identification of the molecular mechanisms underlying CSR. This interdisciplinary project between bioinformatics and immunology aims to shed light onto these mechanisms and highlight differences in physicochemical properties in the B-cell repertoire to identify factors contributing to the decline in immune response with age and its relationships to CSR. The project is developed in line with the hypothesis that effective immune responses, and their resolution, require coordinated action from multiple different subclasses of antibodies. This is enabled by improvements in the high throughput sequencing techniques, which allows the B-cell repertoire to be revealed. The most variable portion of antibody molecules is the third complementarity determining region (CDR3) of the heavy chain. Hence, differences in hydrophobicity, pK value of the C-terminus peptide fragment, and the length of CDR3 were identified and accounted as factors that contribute to the decline in the immune response with age. Our understanding of how the immune response alters with age, is important for research applications in designing tailored vaccine strategies to ensure safety and efficacy. Development of in silico tools for the analysis of the B-cell repertoire is useful in extracting principles and functioning mechanisms that can be tested experimentally, helping in further characterizing CSR.