Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Sustained antibody levels are vital for protective immunity.
• The mechanism for durable antibody maintenance, particularly by long-lived plasma cells (LLPCs) in the bone marrow (BM), is not fully understood.
• It is unclear if BM LLPCs possess unique biology distinct from plasma cells in other tissues.

Purpose of the Study:

• To investigate the role of CD28 in the survival of long-lived plasma cells (LLPCs) and their contribution to long-term antibody titers.
• To determine if BM LLPCs represent a distinct subset with unique survival requirements.

Main Methods:

• Investigated the function of CD28 in LLPC survival in vivo.
• Compared the effects of CD28 loss on BM LLPCs and splenic short-lived plasma cells (SLPCs).
• Assessed the impact of CD28 or its ligands (CD80, CD86) deficiency on LLPC populations and antibody titers.

Main Results:

• CD28 signaling selectively supports the survival of BM LLPCs, but not splenic short-lived plasma cells (SLPCs).
• Loss of CD28 or its ligands significantly reduced the LLPC population and their half-life (from 426 to 63 days).
• Deficiency in CD28 signaling impaired the maintenance of long-term antibody titers.

Conclusions:

• Establishes BM LLPCs as a distinct subset crucial for sustaining antibody titers.
• Uncovers a critical role for CD28 signaling in plasma cell longevity and long-term humoral immunity.
• CD28 is essential for maintaining protective antibody levels through LLPC survival.