INTRODUCTION: Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue. BACKGROUND AND OBJECTIVE: We have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. METHODS: We tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. RESULTS: Both the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. DISCUSSION AND CONCLUSION: The results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.

• Klíčová slova
• B lymphocytes, Porcine respiratory and reproductive syndrome virus, T lymphocytes, T-cell precursors, animals, thymocytes,
• MeSH
• atenuované vakcíny MeSH
• imunitní systém MeSH
• prasata MeSH
• protilátky virové MeSH
• reprodukční a respirační syndrom prasat * prevence a kontrola   MeSH
• virus reprodukčního a respiračního syndromu prasat * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• atenuované vakcíny MeSH
• protilátky virové MeSH

Studies in humans and mice indicate the critical role of the surrogate light chain in the selection of the productive immunoglobulin repertoire during B cell development. However, subsequent studies using mutant mice have also demonstrated that alternative pathways are allowed. Our recent investigation has shown that some species, such as pig, physiologically use preferential rearrangement of authentic light chains, and become independent of surrogate light chains. Here we summarize the findings from swine and compare them with results in other species. In both groups, allelic and isotypic exclusions remain intact, so the different processes do not alter the paradigm of B-cell monospecificity. Both groups also retained some other essential processes, such as segregated and sequential rearrangement of heavy and light chain loci, preferential rearrangement of light chain kappa before lambda, and functional κ-deleting element recombination. On the other hand, the respective order of heavy and light chains rearrangement may vary, and rearrangement of the light chain kappa and lambda on different chromosomes may occur independently. Studies have also confirmed that the surrogate light chain is not required for the selection of the productive repertoire of heavy chains and can be substituted by authentic light chains. These findings are important for understanding evolutional approaches, redundancy and efficiency of B-cell generation, dependencies on other regulatory factors, and strategies for constructing therapeutic antibodies in unrelated species. The results may also be important for explaining interspecies differences in the proportional use of light chains and for the understanding of divergences in rearrangement processes. Therefore, the division into two groups may not be definitive and there may be more groups of intermediate species.

• Klíčová slova
• B cell development, B cell receptors, cell differentiation, gene rearrangement, immunoglobulin heavy and light chains,
• MeSH
• alely MeSH
• B-lymfocyty MeSH
• geny pro imunoglobuliny * MeSH
• imunoglobuliny - kappa-řetězce * genetika   MeSH
• myši MeSH
• náhradní lehké řetězce imunoglobulinů genetika   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• imunoglobuliny - kappa-řetězce * MeSH
• náhradní lehké řetězce imunoglobulinů MeSH