B Cell Responses upon Human Papillomavirus (HPV) Infection and Vaccination

Abstract

Infection with human papillomavirus (HPV) is the necessary cause of cervical cancer. Availability of vaccines against HPV makes it a highly preventable disease. HPV vaccines act through type-specific neutralizing antibodies produced by antigen-specific plasma cells known as long-lived plasma cells (LLPC). However, just as any other vaccine, success of HPV vaccine is attributed to the immunologic memory that it builds, which is largely attained through generation and maintenance of a class of B cells named memory B cells (Bmem). Both LLPCs and Bmems are important in inducing and maintaining immune memory and it is therefore necessary to understand their role after HPV vaccination to better predict outcomes. This review summarizes current knowledge of B-cell responses following HPV vaccination and natural infection, including molecular signatures associated with these responses.

Keywords: HPV vaccine; anamnestic response; long-lived plasma cells (LLPCs); memory B cells (Bmem).

Figure 1

B cell activation, maturation, and proliferation upon exposure to antigens included in the HPV. Dendritic cells present HPV antigens included in the vaccine to naïve B cells. Binding to HPV antigens by B cell receptors results in B-cell activation and proliferation. Some B cells rapidly differentiate into plasma cells that secrete antibodies. B cells that receive additional signals from CD4⁺ T-follicular helper cells (TfH) express AID which is required for antibody class switching and somatic hypermutation (SHM) of antibody gene sequences. Germinal centers develop, containing activated B cells, activated TfH and dendric cells. It is in the light region of the germinal center that B cells compete for interaction with TfH, B cells with higher affinity receptors bind antigen and present peptides to TfH which in turn provide survival signals that promote further proliferation and continued SHM which takes place in the dark zone. B cells with low affinity receptors that do not receive survival signals undergo apoptosis. B cells can go through repeated rounds of SHM resulting in affinity maturation of the antibody genes, until cells exit as either short-lived plasmablasts, long-lived plasma cells, or memory B cells [Created with BioRender.com (Accessed from January to April 2022)].