Date of Award
Open Access Thesis
Major histocompatibility complex class II (MHCII) are molecules that are essential for B cell activation, as well as clonal competition among activated B cell clones during germinal center (GC) reactions. However, it is unknown to what extent MHCII drives the selection of some clones over others. This is of particular importance since MHCII is highly polymorphic with the ability to indirectly alter gutmicrobiome composition by altering the immunoglobulin A (IgA) repertoire. To study this, we utilized a novel triple-transgenic mouse model to assess how B-cellintrinsic MHCII influences GC responses and GC clonal diversity, with an eyeforward to understanding the relevance of this on host-microbiome interactions. Using multiphoton confocal imaging and flow cytometry we show that upon activation, ablation of MHCII expression in B cells leads to the loss of GC formation and a decrease in clonal diversity due to the lack of affinity maturation and competition. Whereas total GC B cell abundance appears to be unaltered, we observed a decrease in the generation of short-lived plasma cells (SLPCs) in gut lymphoid tissues and an increase in the percentage of gut bacteria that were bound by IgA. Collectively, these findings validate the use of the Brainbow mouse model for the study of MHCII’s effects on B cell clonality and point towards its possible role in SLPC development and anti-commensal IgA responses.
Hall, N.(2021). Study of the Effect of B-Cell-Intrinsic Mhcii Antigen Presentation on Germinal Center B Cell Evolution Using The Brainbow Mouse Model. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/6573
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