SARS-CoV-2 infection promotes α4β1 integrin expression in human memory B cells, enhancing their migratory potential toward inflamed respiratory tissues. These findings reveal how antigenic experience shapes tissue-homing immunity and inform vaccine strategies designed to improve mucosal protection.
ABSTRACT
Integrins are critical regulators of lymphocyte adhesion and migration, shaping immune responses by directing cells to specific tissues. In B cells, integrin expression is dynamically regulated during differentiation and activation, yet it is incompletely understood whether immunization and infection influence these pathways. Here, we investigated the expression and regulation of the α4β1 and α4β7 integrins across circulating human B-cell subsets in adults and children following SARS-CoV-2 vaccination and/or infection. By combining flow cytometry, bulk and paired single-cell RNA and VDJ sequencing, and antigen-specific analyses, we show that naïve and early memory B cells predominantly express β7, while antigen experience drives the emergence of two integrin-imprinted memory lineages characterized by β7 or β1 expression. The highest integrin levels were observed in activated memory B cells (actMBCs) and plasmablasts, indicating enhanced migratory potential. Integrin expression was linked both to the maturation stage and to the immunoglobulin isotype. Importantly, SARS-CoV-2 infection—either before or after vaccination—significantly increased the frequency of β1-expressing memory B cells in both adults and children, particularly among spike-specific actMBCs. Single-cell analyses further identified distinct actMBC subsets with divergent integrin profiles and activation dynamics. Together, our findings demonstrate that respiratory viral infection imprints durable migratory programs on antigen-specific B cells, favoring α4β1 expression, with implications for tissue targeting and the design of next-generation mucosal vaccines.