Resident Memory B Cells

Abstract

In mammals, adaptive immunity is mediated by a broadly diverse repertoire of naive B and T lymphocytes that recirculate between secondary lymphoid organs. Initial antigen exposure promotes lymphocyte clonal expansion and differentiation, including the formation of memory cells. Antigen-specific memory cells are maintained at higher frequencies than their naive counterparts and have different functional and homing abilities. Importantly, a subset of memory cells, known as tissue-resident memory cells, is maintained without recirculating in nonlymphoid tissues, often at barrier surfaces, where they can be reactivated by antigen and rapidly perform effector functions that help protect the tissue in which they reside. Although antigen-experienced B cells are abundant at many barrier surfaces, their characterization as tissue-resident memory B (BRM) cells is not well developed. In this study, we describe the characteristics of memory B cells in various locations and discuss their possible contributions to immunity and homeostasis as bona fide BRM cells.

Keywords: memory B cell; mucosal immunity; tissue-resident memory; tissue-specific immunity.

FIG. 1.

Parabiosis allows the identification of resident memory cells. Mice that can be distinguished by a congenic allele (i.e., CD45.1 and CD45.2) are initially infected/immunized to generate memory B cells. Once memory B cells are established, the mice are surgically joined at the skin and allowed to heal. Joint circulation is established in about 10 days and after that point, circulating cells will consist of a 50:50 mix of cells from each partner. Tissue-resident cells will not reach equilibrium between partner mice, resulting in a high host:partner ratio of cells.

FIG. 2.

Resident memory B cells in the skin. The immune cells enter the dermis of the skin through capillary venules and exit through lymphatic vessels. Langerhans cells and resident memory CD8⁺ T cells are maintained in the epidermis. However, most other immune cells, including macrophages (Macs), ILCs, iNKT cells, mast cells, dermal DCs, and helper CD4⁺ T cells, are found in the dermis. Memory B cells reside in the dermis and can be reactivated locally by antigen. DCs, dendritic cells; ILCs, innate lymphoid cells; iNKT, invariant natural killer T.

FIG. 3.

Resident memory B cells are located under the subcapsular sinus in lymph nodes. Circulating and resident memory B cells are found in lymph nodes. At least some of the resident memory B cells reside below the subcapsular sinus. As a result, they are poised to encounter antigens that are delivered from the afferent lymphatic vessels to the subcapsular sinus. Antigens are often captured by subcapsular sinus macrophages, which present antigens to B cells. Memory TFH-like cells also remain in this location and provide help to reactivating memory B cells.

FIG. 4.

Resident memory B cells in the spleen. The open circulation into the spleen allows antigen entry into the red pulp, which is separated from the white pulp or the PALS by the MZ. Some IgM+ memory B cells reside for extended periods in the MZ, where they are poised to encounter blood-borne antigens. Memory B cells also reside in the B cell follicles of the spleen, just outside GCs near memory TFH cells. IgM+ memory B cells are more scattered throughout the B cell follicle. GCs, germinal centers; MZ, marginal zone; PALS, periarteriolar sheath.