Splenic B cells function as immunogenic antigenpresenting cells for the induction of effector T cells

Abstract

Previous studies performed in our laboratory have revealed that an ordered, sequential, tricellular interaction is obligatory for the antigen-driven induction of a specific effector memory T cell. Thus, it was found that antigen-pulsed peritoneal macrophages signal, in spleen cells, the generation of antigen-specific initiator lymphocytes. These lymphocytes, following injection to syngeneic recipients, recruit, in the draining lymph nodes, "virgin" antigen-reactive T lymphocytes. Although the nature of the first and last cell in the interacting sequence was well characterized, the identity of the intermediary initiator splenic cell was obscure. Studies were carried out to characterize the nature of the splenic initiator cells. It was found that spleen cells from nu/nu, adult thymectomized and neonatal thymectomized, or spleen cells from normal donors which had been subjected to cytolysis using anti-Thy-1.2 antibodies in the presence of complement, did generate, following interaction with keyhole limpet hemocyanin (KLH)-fed macrophages, specific initiator cells. Carrageenan impairment of spleen macrophages did not affect the generation of initiator cells, nor did the depletion of dendritic cells from the spleen. On the other hand highly enriched B cell, but not highly enriched T cell populations, when seeded on KLH-pulsed macrophages, generated antigen-specific initiators, which, in vivo, recruited antigen-reactive T cells. It thus appeared that B lymphocytes can function as intermediary obligatory antigen-presenting cells and actively transfer immunogenic signals from peritoneal antigen-presenting cells to T lymphocytes. These findings may therefore suggest that antigen-specific B cells do not function solely as antibody-producing cells, but, once activated by macrophages, may control the induction and differentiation of some antigen-reactive T cell subsets. Thus, one can view the B cell as an important regulatory cell of both cellular and humoral immune functions. The significance of this observation with regard to Ir gene control at the level of B lymphocytes is discussed.

B cells modulate T cells so as to favour T helper type 1 and CD8+ T‐cell responses in the acute phase of Trypanosoma cruzi infection

“…The expansion of antigen‐specific B cells during an immune response allow a large number of these cells to capture and concentrate small amounts of antigens providing efficacious antigen presentation for T cells 48,49 . In fact, the relationship between CD4 + T cells and B cells is relatively well known and B cells are described to be important in the generation of memory/activated effector CD4 + T cells in many different models 13,50–53 . However, the activation and differentiation of CD8 + T cells by B cells is less well documented and B lymphocytes are apparently important in the contraction phase of CD8 + T cell responses, being implicated in the long‐term survival of effector CD8 + T cells 54–56 .…”

Inhibition of Antigen Trafficking through Scavenger Receptor A

“…Current understanding suggests that, when environmental or signaling cues are conducive, the first antigen-presenting cell subset to acquire antigen (Ag) 3 can have a directing role in shaping immune response outcome (1,2). Although innate systems ensure that some foreign Ags are detected and targeted quickly, most Ags require a more fine-tuned trafficking pathway dependent on Ag type and anatomical location.…”

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

“…An H-21-positive AP peritoneal MQ initiates the chain reaction 1161. Such an immunogenic MQ signals a SCthe initiator lymphocytewhich was recently defined by us as a B cell [17]. This initiator splenic B cell functions as an intermediary APC, which finally recruits a virgin antigen-specific T cell.…”

“…We suggest that in these experiments a primary target for the anti-p antibodies is the initiator spleen lymphocyte. We have recently demonstrated [17] that this initiator lymphocyte is a H-21' Ig' B cell of the spleen which functions as an intermediary APC, transferring the specific immunogenic signal from the peritoneal APC to the virgin T cell. The AP capacity of B cells was also demonstrated using neoplastic B cells [18-211. These were shown to present antigen either to normal T lymphocytes, or to antigen-specific T cell lines.…”