Low-affinity B cells transport viral particles from the lung to the spleen to initiate antibody responses

Abstract

The lung is an important entry site for pathogens; its exposure to antigens results in systemic as well as local IgA and IgG antibodies. Here we show that intranasal administration of virus-like particles (VLPs) results in splenic B-cell responses with strong local germinalcenter formation. Surprisingly, VLPs were not transported from the lung to the spleen in a free form but by B cells. The interaction between VLPs and B cells was initiated in the lung and occurred independently of complement receptor 2 and Fcγ receptors, but was dependent upon B-cell receptors. Thus, B cells passing through the lungs bind VLPs via their B-cell receptors and deliver them to local B cells within the splenic B-cell follicle. This process is fundamentally different from delivery of blood or lymph borne particulate antigens, which are transported into B cell follicles by binding to complement receptors on B cells.trafficking | vaccine

Functionally responsive self‐reactive B cells of low affinity express reduced levels of surface IgM

“…It is plausible that polyreactivity enhances Ab or BCR binding of the widely spaced HIV spike proteins, as suggested by the authors. Finally, we speculate that the ability of B cells with low‐affinity receptors for viral antigens to efficiently transport virus‐like particles from the lung to the spleen, as shown by Bessa et al., might have been facilitated by polyreactive B cells possessing an IgM lo phenotype . These reports provide insight into potential benefits afforded by maintaining BCR with degrees of polyreactivity in the immunocompetent B cell repertoire.…”

B Cell‐mediated Antigen Transport to Splenic Follicles

“…Generally, antigen transport in lymph nodes is better understood than in the spleen, mostly because lymph nodes are more accessible to visualization. Here, we highlight recent observations which demonstrate that antigens can enter splenic follicles with the help of B cells in three different ways: via the low-affinity receptor for IgE (CD23) [3], via the B cell receptor (BCR) [4] and via the complement receptors CD21/CD35 [5,6] (Fig. 1).…”

“…3. Low-affinity B cells in the lung bind virus administered intranasally and transport it via the blood to follicles [4]. 1111/sji.12125 .................................................................................................................................................................. found in splenic B cell follicles, but not in other areas of the spleen.…”

Virus-like particle vaccines: immunology and formulation for clinical translation

“…Potent stimulation through BCR crosslinking can override inherent tolerogenic mechanisms, and can activate unresponsive or anergic B cells [106]. Highly repetitive structures also promote binding to low-affinity BCRs through multivalent, or highavidity interactions [107].…”