TY - JOUR
T1 - DNAJA3 regulates B cell development and immune function
AU - Sayson, Stephanie L.
AU - Fan, Jia Ning
AU - Ku, Chien Liang
AU - Lo, Jeng Fan
AU - Chou, Shiu Huey
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - Background: DnaJ homolog subfamily A member 3 (DNAJA3), also known as the tumorous imaginal disc (Tid1), is shown to be crucial in T cell development. DNAJA3 functions as a tumor suppressor implicated in lymphocyte development and survival. However, the role of DNAJA3 in B cell development and immune function remains unknown. In this study, we utilized a mouse model of B cell-specific DNAJA3 knockout (CD19-Cre/+; DNAJA3flx/flx) to investigate the physiological function of DNAJA3 in B cell development and immune function. Methods: We characterized B cell populations in various developmental stages and examined mitochondrial content and function between control and DNAJA3 KO using flow cytometry analysis. DNAJA3 and OXPHOS protein complexes in sorted B cells between mice groups were compared using immunoblot techniques. The activity of B cell blastogenesis in splenocytes was measured by performing CFSE and MTT assays. Furthermore, immunoglobulin production was detected using the ELISA method. Results: DNAJA3 deficiency decreases from pro B cells to immature B cells. The overall B220+ population in the bone marrow and secondary immune organs also decreased. B cell subpopulations B1 (B1b) and B2 significantly decrease. The B cell blastogenesis activity and immunoglobulin production decreased in DNAJA3 KO mice. Mechanistically, DNAJA3 deficiency significantly increases dysfunctional mitochondria activity and decreases mitochondrial mass, membrane potential, and mitochondria respiratory complex proteins. These factors could have influenced B cell differentiation during development, differentiation to antibody-secreting cells, and immune activation. Conclusion: Overall, our study provides supportive evidence for the role of DNAJA3 in B cell development and function.
AB - Background: DnaJ homolog subfamily A member 3 (DNAJA3), also known as the tumorous imaginal disc (Tid1), is shown to be crucial in T cell development. DNAJA3 functions as a tumor suppressor implicated in lymphocyte development and survival. However, the role of DNAJA3 in B cell development and immune function remains unknown. In this study, we utilized a mouse model of B cell-specific DNAJA3 knockout (CD19-Cre/+; DNAJA3flx/flx) to investigate the physiological function of DNAJA3 in B cell development and immune function. Methods: We characterized B cell populations in various developmental stages and examined mitochondrial content and function between control and DNAJA3 KO using flow cytometry analysis. DNAJA3 and OXPHOS protein complexes in sorted B cells between mice groups were compared using immunoblot techniques. The activity of B cell blastogenesis in splenocytes was measured by performing CFSE and MTT assays. Furthermore, immunoglobulin production was detected using the ELISA method. Results: DNAJA3 deficiency decreases from pro B cells to immature B cells. The overall B220+ population in the bone marrow and secondary immune organs also decreased. B cell subpopulations B1 (B1b) and B2 significantly decrease. The B cell blastogenesis activity and immunoglobulin production decreased in DNAJA3 KO mice. Mechanistically, DNAJA3 deficiency significantly increases dysfunctional mitochondria activity and decreases mitochondrial mass, membrane potential, and mitochondria respiratory complex proteins. These factors could have influenced B cell differentiation during development, differentiation to antibody-secreting cells, and immune activation. Conclusion: Overall, our study provides supportive evidence for the role of DNAJA3 in B cell development and function.
KW - B cell development
KW - DNAJA3
KW - Mitochondria complex proteins
KW - Mitochondria dysfunction
KW - Tid1
UR - http://www.scopus.com/inward/record.url?scp=85185195027&partnerID=8YFLogxK
U2 - 10.1016/j.bj.2023.100628
DO - 10.1016/j.bj.2023.100628
M3 - Article
C2 - 37487907
AN - SCOPUS:85185195027
SN - 2319-4170
VL - 47
JO - Biomedical Journal
JF - Biomedical Journal
IS - 2
M1 - 100628
ER -