PMID- 17127633 OWN - NLM STAT- MEDLINE DCOM- 20070404 LR - 20131213 IS - 1369-3786 (Print) IS - 1369-3786 (Linking) VI - 44 IP - 8 DP - 2006 Dec TI - B1 cells contribution to susceptibility in experimental paracoccidioidomycosis: immunoglobulin isotypes and repertoire determination. PG - 755-66 AB - Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. The experimental murine model has been used to approach the disease, with susceptible and resistant mice strains that reproduce most of the main human immunological features. Since the hypergammaglobulinemia observed in susceptible mice and humans might have an influence on B1 cells, we investigated its role during the experimental infection with Paracoccidiodes brasiliensis. CBA/Nxid mice, deficient in B1 cells, and CBA/Nxid reconstituted with B1 cells isolated from the non-mutant CBA/J strain were infected with 106 yeast forms of P. brasiliensis. At the 8th and 22nd week post infection the DTH response of CBA/Nxid mice was significantly higher after 24 h of P. brasiliensis antigens inoculation and the specific humoral response was reduced, in comparison to CBA/J or recCBA/Nxid. Production of NAbs is a hallmark of the B1 subset. Higher Ig productions to auto antigens such as DNA, MBP and RBC were observed in CBA/J infected mice or recCBA/Nxid. Anti P. brasiliensis IgG2a was produced by CBA/Nxid mice early in infection, while CBA/J or recCBA/Nxid presented increased levels of this isotype only after the 8th week of infection. Furthermore, western blotting analysis showed that CBA/Nxid mice expanded less clones against P. brasiliensis antigens, with weakly detectable anti-gp43 antibodies while CBA/J mice produce IgM anti-gp43 at the 2nd week of infection and IgG anti-gp43 at the 2nd and 8th week. On the other hand, recognition of gp70, a fungal antigen that, as gp43, inhibits macrophage activation was not compromised in B1 deficient mice. These results suggest that B1 cells might have influence in the kinetic of production of protective isotypes of immunoglobulins and their repertoire that could contribute to an early drive towards a Th2 response, affecting the cellular response in susceptible mice during experimental paracoccidiodomycosis. FAU - Marcelino Franca, Karla AU - Marcelino Franca K AD - Laboratorio de Biologia do Reconhecer, Centro de Biociencias e Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, RJ, Brazil. FAU - Vericimo, Mauricio A AU - Vericimo MA FAU - Retamal, Claudio AU - Retamal C FAU - Kipnis, Thereza L AU - Kipnis TL FAU - Arnholdt, Andrea C V AU - Arnholdt AC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Med Mycol JT - Medical mycology JID - 9815835 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Antibodies, Fungal) RN - 0 (Antigens, Fungal) RN - 0 (Fungal Proteins) RN - 0 (Glycoproteins) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin Isotypes) RN - 0 (Immunoglobulin M) SB - IM MH - Animals MH - Antibodies, Fungal/*blood MH - Antigens, Fungal/immunology MH - B-Lymphocyte Subsets/*immunology MH - Blotting, Western MH - Disease Models, Animal MH - *Disease Susceptibility MH - Enzyme-Linked Immunosorbent Assay MH - Fungal Proteins/immunology MH - Glycoproteins/immunology MH - Hypersensitivity, Delayed MH - Immunoglobulin G/blood MH - Immunoglobulin Isotypes/*blood MH - Immunoglobulin M/blood MH - Male MH - Mice MH - Mice, Inbred CBA MH - Paracoccidioides/*immunology MH - Paracoccidioidomycosis/*immunology EDAT- 2006/11/28 09:00 MHDA- 2007/04/05 09:00 CRDT- 2006/11/28 09:00 PHST- 2006/11/28 09:00 [pubmed] PHST- 2007/04/05 09:00 [medline] PHST- 2006/11/28 09:00 [entrez] AID - M60212L627711772 [pii] AID - 10.1080/13693780601009485 [doi] PST - ppublish SO - Med Mycol. 2006 Dec;44(8):755-66. doi: 10.1080/13693780601009485.