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Related Concept Videos

Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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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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Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity.

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Long-lived plasma cells (LLPCs) are sessile and cluster in bone marrow niches, regulated by APRIL. Their unique phenotype, including CXCR4 expression, is crucial for maintaining antibody titers and immune memory.

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CXCR4antibodybone marrowimmunologyinflammationlong-lived plasma cellsmousemultiphotonvaccination

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Durable serological memory relies on long-lived plasma cells (LLPCs).
  • Factors governing LLPC generation and survival are not fully understood.

Purpose of the Study:

  • To investigate the characteristics and regulation of LLPCs.
  • To determine the role of specific cell surface molecules in LLPC function and survival.

Main Methods:

  • Intravital two-photon imaging to observe LLPCs in vivo.
  • Deep bulk RNA sequencing and flow cytometry for phenotyping.
  • Conditional gene deletion (Cxcr4) in plasma cells.

Main Results:

  • LLPCs are sessile, APRIL-dependent clusters in the bone marrow, distinct from other plasma cells.
  • LLPCs exhibit a unique transcriptome and express specific surface molecules (CD93, CD81, CXCR4, CD326, CD44, CD48) for adhesion and homing.
  • Cxcr4 deletion in plasma cells caused rapid BM mobilization, reduced PC survival, and faster antibody decay.
  • LLPC B cell receptor repertoire shows reduced diversity and increased public clones, suggesting non-random specification.
  • Aging correlates with LLPC enrichment in the bone marrow, potentially limiting new plasma cell entry.

Conclusions:

  • LLPCs possess unique properties and a distinct molecular signature essential for long-term humoral immunity.
  • CXCR4 is critical for LLPC retention in the bone marrow and sustained antibody production.
  • LLPC generation may be a non-random process, and their accumulation with age could impact immune responses.