<p>IgG, IgM and IgE in complex with antigen have the capacity to regulate specific immune responses. In this investigation, the role of Fc receptors for IgG (FcγRI, FcγRII and FcγRIII) and complement receptors 1 and 2 (CR1/2) for antibody-mediated enhancement of antibody responses are investigated.</p><p>IgM is known to efficiently activate complement and thereby enhance specific antibody responses but it is not known if this involves binding to CR1/2. Using CR1/2 deficient mice, immunized with sheep erythrocytes alone or together with specific IgM, we present evidence that IgM-mediated enhancement is completely dependent on CR1/2 expression, whereas IgG or IgE in complex with bovine serum albumin (BSA) induce strong antibody responses in CR1/2-deficient mice. Enhancement by IgE is mediated via the low affinity receptor for IgE (FcεRII, CD23). However, the receptors which are involved in IgG-mediated enhancement are not known. We find that γ-chain-deficient mice (lacking FcγRI and FcγRIII) have impaired antibody responses to IgG/BSA complexes. In contrast, FcγRIII deficient mice have normal responses, suggesting that FcγRI mediates the effect. Furthermore, IgG/BSA complexes induce up to 189-fold stronger antibody responses in FcγRIIB-deficient mice than in wild-type mice. The threshold dose of IgG/BSA required was lower, the response was sustained for longer and initiated earlier in FcγRIIB-deficient than in wild-type animals. The findings suggest that FcγRIIB acts as a "safety-valve" preventing excessive antibody production during an immune response. We show for the first time that IgG3/BSA complexes can mediate enhancement of specific antibody responses. Their effect does not involve known Fcγ receptors.</p>

IgG, IgM and IgE in complex with antigen have the capacity to regulate specific immune responses. In this investigation, the role of Fc receptors for IgG (FcγRI, FcγRII and FcγRIII) and complement receptors 1 and 2 (CR1/2) for antibody-mediated enhancement of antibody responses are investigated. IgM is known to efficiently activate complement and thereby enhance specific antibody responses but it is not known if this involves binding to CR1/2. Using CR1/2 deficient mice, immunized with sheep erythrocytes alone or together with specific IgM, we present evidence that IgM-mediated enhancement is completely dependent on CR1/2 expression, whereas IgG or IgE in complex with bovine serum albumin (BSA) induce strong antibody responses in CR1/2-deficient mice. Enhancement by IgE is mediated via the low affinity receptor for IgE (FcεRII, CD23). However, the receptors which are involved in IgG-mediated enhancement are not known. We find that γ-chain-deficient mice (lacking FcγRI and FcγRIII) have impaired antibody responses to IgG/BSA complexes. In contrast, FcγRIII deficient mice have normal responses, suggesting that FcγRI mediates the effect. Furthermore, IgG/BSA complexes induce up to 189-fold stronger antibody responses in FcγRIIB-deficient mice than in wild-type mice. The threshold dose of IgG/BSA required was lower, the response was sustained for longer and initiated earlier in FcγRIIB-deficient than in wild-type animals. The findings suggest that FcγRIIB acts as a "safety-valve" preventing excessive antibody production during an immune response. We show for the first time that IgG3/BSA complexes can mediate enhancement of specific antibody responses. Their effect does not involve known Fcγ receptors.

Thesis summary The process of B cell lymphogenesis in swine remains uncertain. Some reports indicate that pigs belong to a group of animal that use ileal Peyers's patches (IPP) for the generation of B cells while others point to the possibility that the bone marrow is functional throughout life. The functional subpopulations of B cells in swine are also unknown. Together with other ruminants, and also birds, γδ T cells in swine may account for >70% of all T cells which is in apparent contrast with humans and mice. The purpose of this thesis was to address these discrepancies and unresolved issues. The results disprove the existing paradigm that the IPP is primary lymphoid tissue and that B cells develop in IPP in an antigen-independent manner. On the other hand, it shows that bone marrow is fully capable of B cell lymphogenesis and remains active at least for the same period of time as it had been speculated for the IPP. This thesis also identified functionally different subsets of porcine peripheral B cells, and shows that CD21 molecules can be expressed in differential forms. Finally, this thesis identifies two lineages of γδ T cells that differ in many functional and phenotype features. This finding may explain why γδ T cells constitute of minority of lymphocytes in circulation of humans and mice.