Defective induction of antigen‐reactive proliferating T cells in B cell‐deprived mice II. Anti‐μ treatment affects the initiation and recruitment of T cells

Abstract

Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.

B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide

“…However, later studies suggested that antiIgM-treated animals were defective in other aspects of the immune response, including T cell activity, making interpretation of the original studies difficult [15][16][17]. A role for Ab in the EAE/MS disease process was indicated by studies in a marmoset EAE model in which Ab to MOG were required for demyelination [11], and in rodent EAE models in which a mAb recognizing the MOG protein enhanced demyelination [10].…”

A two-step, two-signal model for the primary activation of precursor helper T cells

“…Some observations support the likelihood of a central involvement of antigen-specific B cells in pTh activation (48)(49)(50)(51)(52), whereas others do not (e.g., ref. 53).…”

Graft-versus-host disease

“…61,62,66,67 B cells play a critical role in murine models of chronic GVHD; newborn mice rendered B celledeficient by anti-antibody treatment targeting B cell precursors are unable to mount a T cell proliferative response. [68][69][70][71][72] Using this B cell depletion model, Schultz et al 73 revealed a decreased incidence of acute GVHD in animals depleted of B cells. 73 In these studies, both mature T and B cells from donor mice were required for chronic GVHD development.…”