Characterization of the B1 Cell Repertoire in Sickle Cell Disease Pre- and Post-Pneumococcal Vaccination 2258731

Abstract

Abstract Introduction Rationale: Patients with sickle cell disease (SCD) are 600 times more susceptible to S. pneumoniae infections than the general population. This increased risk is mainly attributed to the absence of a functional spleen in SCD patients. However, those with SCD remain more susceptible than those without a functional spleen for reasons unrelated to SCD. Although vaccination has helped counteract this increased risk, pneumococcal infection remains a significant threat to patients with SCD. CD5+B1a cells produce natural antibodies that provide immediate protection against pneumococcal infections, whereas CD5-B1b cells produce protective adaptive antibodies in response to pneumococcal vaccination. Methods We examined the peritoneal and splenic CD5+B1a and CD5-B1b cell repertoires pre- and post-vaccination with Pneumovax23 (PPSV23) in mice with sickle cell disease (Townes model) and compared them with healthy controls. PPSV23 is a native vaccine that covers 23 pneumococcal serotypes and elicits a T-cell-independent response. CD5+B1a and CD5-B1b cells were single-cell sorted from mice with SCD and healthy controls (wild type) pre- and 14 days post-PPSV23 vaccination. The variable heavy chain (IgM) was amplified by PCR and sequenced. Results Single-cell BCR repertoire analysis demonstrated significant differences in VH use (notably VH11 and VH12) and the number of N-region additions (more N-additions pre- and post-vaccination in SCD mice) between wild-type and SCD mice. In mice with SCD, B1 cells over-utilized different identical CDR-H3 sequences compared to wild-type mice. Conclusion Our results revealed significant differences in the pre- and post-PPSV23 vaccination repertoire of B1 cells in SCD mice compared to healthy mice, offering insights into the effectiveness of pneumococcal vaccination in SCD. These results provide a rationale for optimizing vaccine strategies and developing targeted immunotherapies to enhance immune protection in patients with SCD. Funding Source Research reported was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R03AI123875. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)