Characterizing the distribution of the murine T cell receptor repertoire in splenic T and B cell zones during an immune response
The adaptive immune system recognizes billions of unique antigens using highly variable T cell receptors (TCRs). However, little is known regarding the compartmentalization of TCR repertoires (TCR-R) within lymphoid organs. This paper studies the differences in TCR-R composition between the T cell zone (TCZ), B cell zone (BCZ), and germinal centers (GC) of the spleen by analyzing the complementarity-determining region 3 of the beta chain (CDR3beta) in microdissected splenic compartments from naive and immunized mice.Despite a lower absolute number of clonotypes in the BCZ, downsampling analysis revealed a highly similar repertoire structure between the BCZ and TCZ, with differences primarily driven by compartment size. After immunization, modeling of clonal expansion using a Galton-Watson process showed early proliferation in the TCZ, later shifting to the BCZ. According to our model, GCs harbored highly expanded T cell clonotypes, and our data showed a reduced overall diversity, suggesting strong clonal selection. This was confirmed by clustering analysis, revealing the presence of highly similar TCR sequences across multiple mice, tracing back to early immune response stages.While clonotype abundance changed over time, sequence characteristics remained stable across compartments. These findings demonstrate that splenic TCR repertoires (TCR-Rs) are shaped predominantly by compartment size and proliferation rates rather than intrinsic differences in sequence properties. By integrating downsampling and proliferation modeling, we provide a quantitative framework for assessing TCR-R dynamics in distinct immune compartments with variable sizes during an immune response.