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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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BOB.1/OBF.1 is required during B-cell ontogeny for B-cell differentiation and germinal center function.

Annika C Betzler1, Katja Fiedler1,2, Thomas K Hoffmann1

  • 1Department of Oto-Rhino-Laryngology, Ulm University Medical Center, Ulm, Germany.

European Journal of Immunology
|December 17, 2021
PubMed
Summary

The transcriptional co-activator BOB.1/OBF.1 is essential for B-cell development and germinal center formation. Its absence causes defects throughout B-cell ontogeny, indicating a cell-intrinsic role in germinal center reactions.

Keywords:
B-cell differentiationBOB.1/OBF.1Germinal centerHumoral immunityTranscriptional co-activator

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Area of Science:

  • Immunology
  • Molecular Biology
  • Transcriptional Regulation

Background:

  • BOB.1/OBF.1 (also known as OBF.1) is a lymphocyte-specific transcriptional co-activator crucial for octamer-dependent gene expression.
  • It collaborates with Oct-1 and Oct-2 transcription factors to regulate genes vital for lymphocyte function.
  • Previous studies using knockout mice indicated BOB.1/OBF.1 is important for both B and T cells, with a notable absence of germinal centers in deficient mice.

Purpose of the Study:

  • To determine the specific developmental stage at which BOB.1/OBF.1 is essential for germinal center formation.
  • To investigate whether defects observed in late B-cell development are solely a consequence of early developmental issues.
  • To elucidate the intrinsic role of BOB.1/OBF.1 within B cells during germinal center reactions.

Main Methods:

  • Development of a conditional knockout mouse model to enable stage-specific deletion of BOB.1/OBF.1.
  • Analysis of B-cell development and germinal center formation following conditional BOB.1/OBF.1 deletion at various stages.
  • Specific deletion of BOB.1/OBF.1 in germinal center B cells to assess its intrinsic function.

Main Results:

  • BOB.1/OBF.1 is required for both early (antigen-independent) and late (antigen-dependent) B-cell development.
  • Efficient germinal center reactions necessitate BOB.1/OBF.1 throughout B-cell ontogeny.
  • Conditional deletion of BOB.1/OBF.1 specifically in germinal center B cells confirmed an intrinsic requirement for germinal center formation.

Conclusions:

  • BOB.1/OBF.1 plays a critical, continuous role from early B-cell development through to germinal center formation.
  • The failure to form germinal centers in BOB.1/OBF.1-deficient mice is an intrinsic defect of germinal center B cells.
  • These findings highlight the non-redundant function of BOB.1/OBF.1 in orchestrating adaptive immune responses mediated by B cells.