Role of germinal centers for the induction of broadly-reactive memory B cells

• Published in: Current opinion in immunology Vol. 45; pp. 119 - 125
• Main Authors: Takahashi, Yoshimasa, Kelsoe, Garnett
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2017
• Subjects: Allergy and Immunology; Animals; Antigens, Viral - immunology; B-Lymphocytes - immunology; Cell Proliferation; Cell Survival - immunology; Epitopes - immunology; Germinal Center - immunology; Germinal Center - virology; Humans; Immunologic Memory; Viruses - immunology
• ISSN: 0952-7915; 1879-0372; 1879-0372
• DOI: 10.1016/j.coi.2017.03.002

•Viral conserved domains are often concealed from the humoral responses.•Memory B cells counteract with viral mutations by germline-encoded cross-reactivity.•GC reactions fine-tune the specificity of memory B cells toward the conserved domains.•Permissive GC selection allows the fine-tuning of memory specificity.•Broadly-reactive B cells may be recruited into the memory pool with an attenuated T-cell help. Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continued survival/proliferation of B cells that bind with low affinity or react to cryptic epitopes, increasing their chance of memory recruitment. In this review, we discuss the adaptive strategies of B-cell memory to viral antigenic variations.