CD19 is essential for B cell activation by promoting B cell receptor–antigen microcluster formation in response to membrane-bound ligand

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

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IL-4 Upregulates Igα and Igβ Protein, Resulting in Augmented IgM Maturation and B Cell Receptor–Triggered B Cell Activation

The Journal of Immunology ◽

10.4049/jimmunol.1203211 ◽

2013 ◽

Vol 191 (2) ◽

pp. 670-677 ◽

Cited By ~ 15

Author(s):

Benchang Guo ◽

Thomas L. Rothstein

Keyword(s):

B Cell ◽

Cell Activation ◽

Cell Receptor ◽

B Cell Receptor ◽

B Cell Activation

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Utilization of a photoactivatable antigen system to examine B-cell probing termination and the B-cell receptor sorting mechanisms during B-cell activation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1517612113 ◽

2016 ◽

Vol 113 (5) ◽

pp. E558-E567 ◽

Cited By ~ 19

Author(s):

Jing Wang ◽

Shan Tang ◽

Zhengpeng Wan ◽

Yiren Gao ◽

Yiyun Cao ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Single Molecule ◽

Cell Activation ◽

Cell Receptor ◽

B Cell Receptor ◽

Antigen Binding ◽

B Cell Activation ◽

Class I Mhc ◽

Antigen System

Antigen binding to the B-cell receptor (BCR) induces several responses, resulting in B-cell activation, proliferation, and differentiation. However, it has been difficult to study these responses due to their dynamic, fast, and transient nature. Here, we attempted to solve this problem by developing a controllable trigger point for BCR and antigen recognition through the construction of a photoactivatable antigen, caged 4-hydroxy-3-nitrophenyl acetyl (caged-NP). This photoactivatable antigen system in combination with live cell and single molecule imaging techniques enabled us to illuminate the previously unidentified B-cell probing termination behaviors and the precise BCR sorting mechanisms during B-cell activation. B cells in contact with caged-NP exhibited probing behaviors as defined by the unceasing extension of membrane pseudopods in random directions. Further analyses showed that such probing behaviors are cell intrinsic with strict dependence on F-actin remodeling but not on tonic BCR signaling. B-cell probing behaviors were terminated within 4 s after photoactivation, suggesting that this response was sensitive and specific to BCR engagement. The termination of B-cell probing was concomitant with the accumulation response of the BCRs into the BCR microclusters. We also determined the Brownian diffusion coefficient of BCRs from the same B cells before and after BCR engagement. The analysis of temporally segregated single molecule images of both BCR and major histocompatibility complex class I (MHC-I) demonstrated that antigen binding induced trapping of BCRs into the BCR microclusters is a fundamental mechanism for B cells to acquire antigens.

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