Majority of human circulating plasmablasts stop blasting: A probable misnomer.

Area of Science:

• Immunology
• Cell Biology

Background:

• Antibody secreting cells (ASC), or plasmablasts, appear in circulation after infection or vaccination.
• A subset of ASC migrate to the bone marrow (BM) to mature into long-lived plasma cells (LLPC).
• LLPC are quiescent, while ASC are generally considered proliferative.

Approach:

• Utilized novel optofluidic technology to assess cell division and Ig secretion simultaneously.
• Evaluated Ki-67 and BrdU incorporation in blood ASC and BM LLPC.
• Analyzed cell division of BM LLPC over 7-21 days in culture.

Key Points:

• Over 95% of nascent blood ASC express Ki-67, but only 6-12% incorporate BrdU.
• Less than 5% of BM LLPC express Ki-67 and show no BrdU uptake.
• Only 11% of early-minted blood ASC undergo division, and no terminally differentiated BM LLPC divide in culture.

Conclusions:

• BM LLPC exhibit complete cell cycle arrest.
• Differentiation into ASC discourages entry into S phase.
• The term "plasmablast" may be a misnomer as most Ki-67+ blood ASC have exited the cell cycle.