Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity
COVID-19 patients show varying severity of the disease ranging from asymptomatic to requiring intensive care. Although a number of SARS-CoV-2 specific monoclonal antibodies have been identified, we still lack an understanding of the overall landscape of B-cell receptor (BCR) repertoires in COVID-19 patients. Here, we used high-throughput sequencing of bulk and plasma B-cells collected over multiple time points during infection to characterize signatures of B-cell response to SARS-CoV-2 in 19 patients. Using principled statistical approaches, we determined differential features of BCRs associated with different disease severity. We identified 38 significantly expanded clonal lineages shared among patients as candidates for specific responses to SARS-CoV-2. Using single-cell sequencing, we verified reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identified natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in a number of patients. Our results provide important insights for development of rational therapies and vaccines against COVID-19.
Code (1)
Similar Papers 제목 키워드 기반
Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies.…
SpecificityTowards a quantitative theory of tolerance
A cornerstone of the classical view of tolerance is the elimination of self-reactive T cells during negative selection in the thymus. However, high-throughput T-cell receptor sequencing data has so far failed to detect s…
Decision MakingNonequilibrium antigen recognition during infections and vaccinations
The immune response to an acute primary infection is a coupled process of antigen proliferation, molecular recognition by naive B cells, and their subsequent proliferation and antibody shedding. This process contains a f…
Variability in the local and global composition of human T-cell receptor repertoires during thymic development across cell types and individuals
The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T cell maturat…
DiversityHow many different clonotypes do immune repertoires contain?
Immune repertoires rely on diversity of T-cell and B-cell receptors to protect us against foreign threats. The ability to recognize a wide variety of pathogens is linked to the number of different clonotypes expressed by…
Diversity