Complement-Activating IgM Enhances the Humoral but Not the T Cell Immune Response in Mice

Abstract

IgM antibodies specific for a certain antigen can enhance antibody responses when administered together with this antigen, a process believed to require complement activation by IgM. However, recent data show that a knock-in mouse strain, Cμ13, which only produces IgM unable to activate complement, has normal antibody responses. Moreover, the recently discovered murine IgM Fc receptor (FcµR or TOSO/FAIM3) was shown to affect antibody responses. This prompted the re-investigation of whether complement activation by specific IgM is indeed required for enhancement of antibody responses and whether the mutation in Cµ13 IgM also caused impaired binding to FcµR. The results show that IgM from Cµ13 and wildtype mice bound equally well to the murine FcµR. In spite of this, specific Cμ13 IgM administered together with sheep red blood cells or keyhole limpet hemocyanine was a very poor enhancer of the antibody and germinal center responses as compared with wildtype IgM. Within seconds after immunization, wildtype IgM induced deposition of C3 on sheep red blood cells in the blood. IgM which efficiently enhanced the T-dependent humoral immune response had no effect on activation of specific CD4+ T cells as measured by cell numbers, cell division, blast transformation, or expression of the activation markers LFA-1 and CD44 in vivo. These observations confirm the importance of complement for the ability of specific IgM to enhance antibody responses and suggest that there is a divergence between the regulation of T- and B-cell responses by IgM.

Marginal Zone B Cells Transport IgG3-Immune Complexes to Splenic Follicles

“…Blood and spleen samples were prepared and stained, as described (11). Briefly, cell suspensions were treated with hypotonic buffer to deplete the RBC, washed in PBS, and resuspended in FACS buffer.…”

“…Spleens were harvested, prepared, and stored, as described (11). Briefly, spleens were embedded in optimal cutting temperature embedding media (Sakura Finetek, Alphen aan den Rijn, the Netherlands), snap frozen in liquid nitrogen, and stored at 280˚C.…”

“…Interestingly, erythrocyte-specific IgM has the opposite effect from IgG and enhances Ab responses to erythrocytes both in humans and animals (4,6). IgM-mediated enhancement requires the presence of C3 and complement receptor (CR)1/2 (7-9) and that IgM is able to activate C (7,10,11). It is well known that lack of C1, C2, C3, C4, and CR1/2 leads to impaired primary as well as secondary Ab responses also to Ag administered alone (12).…”

IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model

“…Contrary to the transfusion of allogeneic mouse RBC that circulate with a normal life span (27,28), SRBC are cleared from circulation within a few hours (29,30).…”

Nomenclature of Toso, Fas Apoptosis Inhibitory Molecule 3, and IgM FcR

“…Kubagawa responded to this concern by providing data showing that mouse FcmR/ Faim3 indeed binds IgM, but it does so only transiently, unlike the constitutive IgM binding by the human receptor. A recent article by Ding et al (21) supporting this observation was cited. In the end, Nolan agreed that he would be amenable to a name change recommended by the consensus.…”