An Hour after Immunization Peritoneal B-1 Cells Are Activated to Migrate to Lymphoid Organs Where within 1 Day They Produce IgM Antibodies That Initiate Elicitation of Contact Sensitivity

Abstract

Elicitation of contact sensitivity (CS), a classic example of T cell-mediated immunity, requires Ag-specific IgM Abs to trigger an initiation process. This early process leads to local recruitment of CS-effector T cells after secondary Ag challenge. These Abs are produced by the B-1 subset of B cells within 1 day after primary skin immunization. In this study we report the surprising observation that B-1 cells in the peritoneal cavity are activated as early as 1 h after naive mice are painted with a contact-sensitizing Ag on the skin of the trunk and feet to begin the initiation of CS. B-1 cells in the spleen and draining lymph nodes produce the initiating Abs by 1 day after immunization, when we found increased numbers of Ag-specific IgM Ab-producing cells in these tissues by ELISPOT assay. Importantly, we show that contact-activated peritoneal B-1 cells migrate to these lymphoid tissues and then differentiate into Ag-specific IgM Ab-producing cells, resulting in specific CS-initiating IgM Abs in the serum by 1 day. Furthermore, pertussis toxin, which is known to inhibit signaling via G protein-coupled chemokines, inhibited the migration of contact-activated peritoneal B-1 cells to the lymphoid tissues, probably due to BLR-1 (Burkitt lymphoma receptor-1). These findings indicate that within 1 h after contact skin immunization, B-1 cells in the peritoneal cavity are activated to migrate to the lymphoid tissues by chemokine-dependent mechanisms to produce serum Ag-specific IgM Abs within 1 day after immunization, leading to local recruitment of CS-effector T cells.

Identification of Initiator B Cells, a Novel Subset of Activation-Induced Deaminase-Dependent B-1-Like Cells That Mediate Initiation of Contact Sensitivity

“…Based on evidence presented here and in our previous studies (3), we know that cells in the PerC, like B-1 cells, express CD11b. Although it is clear that CD5 expression can be used to enrich for PerC cells with initiator activity, it may not define the population because we previously found that transfer of either CD5 ϩ or CD5 Ϫ CD11b ϩ PerC cells could transfer initiation (1,3). CD5 expression may be induced or further up-regulated on initiator B cells activated by sensitization, as all B cells are capable of expressing CD5 when activated (10,11).…”

“…These Abs enter the circulation and, upon local challenge to the skin, induce a mild, local vasoactive response that peaks 2 h after challenge (7,8). Evidence suggests that this early response is required to recruit rare Agspecific T cells to the local site of exposure, since interference with any step in this pathway or with mechanisms of T cell recruitment within the 2-h window postchallenge, effectively prevents the subsequent development of the severe, delayed inflammatory response (3,4,9). For this reason, the mechanisms responsible for the early response have been termed DTH or CS initiation.…”

“…As naive cells, these reside in the peritoneal cavity (PerC). Following sensitization they are activated to migrate to the spleen and produce IgM (3,5,6). These Abs enter the circulation and, upon local challenge to the skin, induce a mild, local vasoactive response that peaks 2 h after challenge (7,8).…”

“…1). Central to this pathway is the production of Ag-specific IgM Abs by a population of nonclassical B cells (2)(3)(4). As naive cells, these reside in the peritoneal cavity (PerC).…”

B‐1a cells are imprinted by the microenvironment in spleen and peritoneum

“…On the other hand, a clear influence of the spleen on peritoneal B-1a cells is known. Splenectomy results in a severe loss of peritoneal B-1a cells [8,9] and more recently, it has been demonstrated that upon appropriate antigen challenge specific peritoneal B-1a cells quickly migrate to the spleen [23].…”