PTEN restricts IL-21R signaling in GC B cells and suppresses their differentiation to plasma cells.

The germinal center (GC) reaction is essential for generating high-quality humoral memory. Positively selected GC B cells must decide whether to remain in the GC for further affinity maturation or differentiate into memory or plasma cells (PCs). Previously, we identified IL-21R and CD40 signaling as critical promoters of GC B cell effector differentiation.

BLIMP1 controls GC B cell expansion and exit through regulating cell cycle progression and key transcription factors BCL6 and IRF4.

In B cells, BLIMP1 is required for plasma cell differentiation. BLIMP1 is also expressed in some germinal center (GC) B cells (GCBC), yet the role of BLIMP1 in GCBC is not understood. Here we generated mixed bone marrow (BM) chimeric mice using Prdm1 CD19 and Prdm1 CD19 BM, allowing us to examine the cell-intrinsic functions of BLIMP1 in GCBC, independent of antibody or antigen levels.

IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells.

Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (T)-derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to induce c-MYC and p-S6 in GCBCs.

Surface phenotypes of naive and memory B cells in mouse and human tissues.

Memory B cells (MBCs) protect the body from recurring infections. MBCs differ from their naive counterparts (NBCs) in many ways, but functional and surface marker differences are poorly characterized. In addition, although mice are the prevalent model for human immunology, information is limited concerning the nature of homology in B cell compartments.

Roles of Bone Morphogenetic Protein Receptor 1A in Germinal Centers and Long-Lived Humoral Immunity.

In response to T-dependent Ag, germinal centers (GC) generate bone marrow-resident plasma cells (BMPC) and memory B cells (MBC). In this study, we demonstrate that the bone morphogenetic protein receptor 1A (BMPR1A) signaling pathway, which regulates differentiation and self-renewal in multiple stem cell populations, regulates GC dynamics and resultant establishment of BMPC and MBC. Expression studies using quantitative PCR and novel IRES.

A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice.

Optimal vaccines are needed for sustained suppression of SARS-CoV-2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS-CoV-2 S1 subunit antigen (Ad5.SARS-CoV-2-S1) for COVID-19 immunization and evaluated its immunogenicity in mice.

Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis.

Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy.