{Reference Type}: Journal Article
{Title}: Single-cell 5' RNA sequencing of camelid peripheral B cells provides insights into cellular basis of heavy-chain antibody production.
{Author}: Yi L;Guo X;Liu Y;Jirimutu ;Wang Z;
{Journal}: Comput Struct Biotechnol J
{Volume}: 23
{Issue}: 0
{Year}: 2024 Dec
{Factor}: 6.155
{DOI}: 10.1016/j.csbj.2024.04.041
{Abstract}: Camelids produce both conventional tetrameric antibodies (Abs) and dimeric heavy-chain antibodies (HCAbs). Although B cells that generate these two types of Abs exhibit distinct B cell receptors (BCRs), whether these two B cell populations differ in their phenotypes and developmental processes remains unclear. Here, we performed single-cell 5' RNA profiling of peripheral blood mononuclear cell samples from Bactrian camels before and after immunization. We characterized the functional subtypes and differentiation trajectories of circulating B cells in camels, and reconstructed single-cell BCR sequences. We found that in contrast to humans, the proportion of T-bet+ B cells was high among camelid peripheral B cells. Several marker genes of human B cell subtypes, including CD27 and IGHD, were expressed at low levels in the corresponding camel B cell subtypes. Camelid B cells expressing variable genes of HACbs (VHH) were widely present in various functional subtypes and showed highly overlapping differentiation trajectories with B cells expressing variable genes of conventional Abs (VH). After immunization, the transcriptional changes in VHH+ and VH+ B cells were largely consistent. Through structure modeling, we identified a variety of scaffold types among the reconstructed VHH sequences. Our study provides insights into the cellular context of HCAb production in camels and lays the foundation for developing single-B cell-based camelid single-domain Ab screening.