Circulating T_FH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell...

Area of Science:

• Immunology
• Vaccinology
• Cellular Biology

Background:

• Inactivated influenza vaccine (IIV) is crucial for seasonal influenza prevention.
• IIV stimulates B cells and T follicular helper (T_FH) cells, leading to antibody production.
• The precise human cellular immune responses to IIV are not fully understood.

Purpose of the Study:

• To comprehensively analyze B cell and T cell immune responses following IIV in healthy adults.
• To characterize the quantity, phenotype, and isotype of influenza-specific B cells.
• To investigate the role of T_FH cells and the location of vaccine-induced B cells.

Main Methods:

• Analysis of B cell and T cell responses in 35 healthy adults after IIV.
• Use of recombinant hemagglutinin (rHA) probes to identify influenza-specific B cells.
• Assessment of cell populations (e.g., T_FH, memory B cells) and antibody titers.
• Examination of B cell distribution across seven human tissue compartments.

Main Results:

• IIV induced a three-pronged B cell response: transient antibody-secreting B cells, CD21^hiCD27⁺ memory B cells, and CD21^loCD27⁺ B cells.
• Circulating T_FH cell activation correlated with memory B cell development.
• Preexisting antibodies could limit serum antibody titer increases; vaccine-induced B cells were not sustained in peripheral blood at 1 year.
• Influenza-specific memory B cells were predominantly found in secondary lymphoid tissues and lungs.

Conclusions:

• Understanding T_FH cell dynamics, preexisting serological memory, and tissue compartmentalization is vital for designing effective universal influenza vaccines.
• Future vaccine strategies should aim to optimize B cell immunity by considering these factors.
• Improved targeting of cellular T cell immunity is also a goal for enhanced vaccine efficacy.