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Review
. 2024 Apr 16;12(8):1981-2006.
doi: 10.1039/d3bm01841e.

Biomaterial engineering strategies for B cell immunity modulations

Ali Zareein  1   2 , Mina Mahmoudi  1   2 , Shruti Sunil Jadhav  1 , Joel Wilmore  3 , Yaoying Wu  1   2   3
Affiliations
Review

Biomaterial engineering strategies for B cell immunity modulations

Ali Zareein et al. Biomater Sci. .

Abstract

B cell immunity has a penetrating effect on human health and diseases. Therapeutics aiming to modulate B cell immunity have achieved remarkable success in combating infections, autoimmunity, and malignancies. However, current treatments still face significant limitations in generating effective long-lasting therapeutic B cell responses for many conditions. As the understanding of B cell biology has deepened in recent years, clearer regulation networks for B cell differentiation and antibody production have emerged, presenting opportunities to overcome current difficulties and realize the full therapeutic potential of B cell immunity. Biomaterial platforms have been developed to leverage these emerging concepts to augment therapeutic humoral immunity by facilitating immunogenic reagent trafficking, regulating T cell responses, and modulating the immune microenvironment. Moreover, biomaterial engineering tools have also advanced our understanding of B cell biology, further expediting the development of novel therapeutics. In this review, we will introduce the general concept of B cell immunobiology and highlight key biomaterial engineering strategies in the areas including B cell targeted antigen delivery, sustained B cell antigen delivery, antigen engineering, T cell help optimization, and B cell suppression. We will also discuss our perspective on future biomaterial engineering opportunities to leverage humoral immunity for therapeutics.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

Fig. 1
Fig. 1. Overview of B cell responses. (A) Antigens accumulate in dLN following administration. (B) Antigen presentations. Opsonized antigens are acquired by subcapsular sinus macrophages (SSM) from the subcapsular sinus and handed off to follicular dendritic cells (FDC) in the B cell follicle; native CD4+ T cells receive antigen presentation by conventional dendritic cells (cDC) at the paracortex and differentiate into early follicular T helper (Tfh) cells. (C) Antigen-stimulated B cells migrate toward the T–B border to seek cognate interactions with Tfh cells. (D) B cells that received sufficient T cell help spontaneously organize into germinal center (GC) structures that are separated into two distinct components: the light zone (LZ) is composed of LZ B cells, Tfh cells and FDC; the dark zone (DZ) is mainly composed of DZ B cells that undergo somatic hypermutations (SHMs). (E) An overview of the dynamics of GC affinity selection. Prior to GC entry, B cells with a low antigen affinity are excluded from GC entry; relatively high affinity B cells differentiate extrafollicularly into short-lived plasma cells (PCs) and memory B cells (MBCs). Cells with intermediate antigen affinity are often selected to enter GC reactions. GC B cells go through rounds of mutation, selection, and expansion. During the GC reactions, some high-affinity B cells exit as MBCs and long-lived PCs, while low-affinity B cells undergo apoptosis. Other B cells potentially enter into the next rounds of mutation and selection. Eventually the GC retracts and the GC B cell population dwindles.
Fig. 2
Fig. 2. Overview of B cell-targeted antigen delivery strategies. (A) Albumin-binding amph-vaccine accumulates in dLN by albumin hitchhiking. (B) Intranasally delivered amph-vaccines are transported to the nasal associated lymphoid tissue (NALT) through a mucosal epithelial layer mediated by neonatal Fc receptor (FcRn). (C) Highly glycosylated self-assembled HIV nanoparticle antigens activate the mannose-binding lectin (MBL) complement pathway and are acquired by SSM cells from the subcapsular sinus (SCS) for antigen delivery to the B cell follicles. (D) Two-stage nanoparticles accumulate at the SCS (left), and release small-molecule drug to the B cell follicle as the linkers degrade at predetermined kinetics (right). (E) When antigens are administered with CL-lipo or SMNP(left), the SSM barrier cells are depleted and antigens are accumulated in the B cell follicles (right).
Fig. 3
Fig. 3. Overview of sustained antigen delivery for enhanced B cell responses. (A) Bolus administration of vaccine elicits antibody responses with limited diversity, and relatively low Tfh cell responses. (B–D) The sustained delivery of B cell antigens enhances GC reactions, and potentially increases the ratio of LZ B cells and DZ B cells. The breadth of the antibody responses and Tfh cell responses is also improved. Effective sustained antigen delivery strategies include (B) microneedle (MN) patches; (C) hydrogel; and (D) slow administration through exp-inc dosing regimen or an osmotic pump.
Fig. 4
Fig. 4. Overview of current strategies to integrate T cell help for B cell immunity. (A) Self-assembled peptide nanofibers with appended peptide epitopes for both T cells and B cells to elicit T cell help for B cell responses. (B) T cell epitope concentrations carried by nanofibers impact Tfh cell responses and B cell immune responses. In the representative bell curve, the media level of T cell concentration elicits the maximal frequency of Tfh cells. (C) Virus-like particles (VLPs) carrying epitopes for pre-existing T cells can elicit T cell help from pre-existing T cells for B cell responses. (D) Liposomal nanoparticles encapsulate antigens for pre-existing T cells and elicit T cell help for B cell responses against B cell antigens displayed on the nanoparticles.
Fig. 5
Fig. 5. Overview of antigen engineering strategies for B cell responses. (A) Engagement of a single antigen induces limited B cell activation. (B–D) Biomaterial-mediated multivalent antigen presentations promote B cell activations. (B) Multivalent display of antigens along a polymer backbone. (C) Nanoparticle displays multiple B cell antigens on the particle surface. (D) Computationally designed self-assembled enanoparticles. (E) B cell antigen modified with alum-binding peptides carries alum adjuvant to antigen-specific B cells for enhanced immunity.
Fig. 6
Fig. 6. Overview of strategies to suppress antigen-specific B cells. (A) Siglec-engaging tolerance-inducing antigenic liposomes (STAL) display antigens and synthetic siglec CD22L suppresses antigen-specific B cells by engaging inhibitory CD22 receptor and B cell receptor (BCR). (B) Helical polyisocyanopeptide (PIC) and PEGylated cationic liposome (PCL) display both antigens and glycan or peptide CD22L respectively to inhibit B cell functions. (C) Soluble antigen array (SAgA) is designed based on hyaluronic acid (HA) polymers or 4-arm PEG polymers to deliver antigens, myelin sheath peptide antigen (PLP) or insulin, with inhibitory peptide (LABL) for intercellular adhesion molecule-1 (ICAM-1) to inhibit B cell activation.
None
Ali Zareein
None
Mina Mahmoudi
None
Shruti Sunil Jadhav
None
Joel Wilmore
None
Yaoying Wu
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