CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Author:

Huggins Jennifer1,Pellegrin Tina2,Felgar Raymond E.3,Wei Chungwen1,Brown Miguel2,Zheng Bo1,Milner Eric C. B.1,Bernstein Steven H.4,Sanz Ignacio1,Zand Martin S.2

Affiliation:

1. Division of Allergy, Immunology and Rheumatology,

2. Division of Nephrology,

3. Department of Pathology,

4. James P. Wilmot Cancer Center, University of Rochester Medical Center, NY

Abstract

Abstract Unmethylated CpG DNA activation of naive CD27− B cells has been reported to require B-cell–receptor (BCR) cross-linking. We describe a culture system using CpG DNA with sequential steps for T-cell–independent activation of naive CD19+CD27− human peripheral blood B cells that induces efficient CD138+ plasma-cell differentiation. CD27+ and CD27− B cells were cultured in a 3-step system: (1) days 0 to 4: CpG, IL-2/10/15; (2) days 4 to 7: IL-2/6/10/15 and anti-CD40L; (3) days 7 to 10: IL-6/15, IFN-α, hepatocyte growth factor, and hyaluronic acid. Both CD27+ and CD27− B cells up-regulated intracytoplasmic TLR-9 following CpG DNA activation. CD27− B-cell activation required cell-cell contact. Both naive and memory B cells progressed to a plasma-cell phenotype: CD19lowCD20lowCD27+CD38+HLA-DRlow. Seventy percent of the CD27−-derived CD138+ cells demonstrated productive V chain rearrangements without somatic mutations, confirming their origin from naive precursors. Plasma cells derived from CD27+ B cells were primarily IgG+, while those from CD27− B cells were IgM+. Our results indicate that under certain conditions, naive B cells increase TLR-9 expression and proliferate to CpG DNA stimulation without BCR signaling. In addition to its immunologic significance, this system should be a valuable method to interrogate the antigenic specificity of naive B cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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