IL-10–producing B cells, also known as regulatory B cells (Bregs), play a key role in controlling autoimmunity. In this study, we report that chimeric mice specifically lacking IL-10–producing B cells (IL-10−/−B cell) developed an exacerbated arthritis compared with chimeric wild-type (WT) B cell mice. A significant decrease in the absolute numbers of Foxp3 regulatory T cells (Tregs), in their expression level of Foxp3, and a marked increase in inflammatory Th1 and Th17 cells were detected in IL-10−/− B cell mice compared with WT B cell mice. Reconstitution of arthritic B cell deficient (μMT) mice with different B cell subsets revealed that the ability to modulate Treg frequencies in vivo is exclusively restricted to transitional 2 marginal zone precursor Bregs. Moreover, transfer of WT transitional 2 marginal zone precursor Bregs to arthritic IL-10−/− mice increased Foxp3+ Tregs and reduced Th1 and Th17 cell frequencies to levels measured in arthritic WT mice and inhibited inflammation. In vitro, IL-10+/+ B cells established longer contact times with arthritogenic CD4+CD25− T cells compared with IL-10−/− B cells in response to Ag stimulation, and using the same culture conditions, we observed upregulation of Foxp3 on CD4+ T cells. Thus, IL-10–producing B cells restrain inflammation by promoting differentiation of immunoregulatory over proinflammatory T cells.

Cellular competition for survival signals offers a cogent and appealing mechanism for the maintenance of cellular homeostasis [Raff, M. C. (1992) Nature (London) 356, 397-400]. We present a theoretical and experimental investigation of the role of competition for resources in the regulation of peripheral B cell numbers. We use formal ecological competition theory, mathematical models of interspecific competition, and competitive repopulation experiments to show that B cells must compete to persist in the periphery and that antigen forms a part of the resources over which B cells compete.''The most basic qualities of a natural community are the kinds and numbers of species living in them.'' This quotation from a classic ecological monograph (1) could equally well apply to immunology, where the communities in question are populations of lymphocytes present within individual organisms. Motivated by this similarity in basic questions we have used ecological competition theory in studies of B cell homeostasis and diversity. A combination of laboratory and mathematical models lead us to propose that the size of the peripheral B lymphocyte pool results from a process of immigration from the bone marrow, competition for resources in the periphery (2), and rapid death of cells that fail to secure resources. Our models allow us to quantify the contribution of each of these three processes to the final size of the peripheral B cell pool.Immunologists often use the word competition and most would probably agree that they define competition as ''an interaction between two populations, in which, for each, the birth rates are depressed or the death rates increased by the presence of the other population'' (3). However, this type of interaction can arise through a number of different processes. In resource competition (1) the negative effects come about because the two populations both have a need for the same substrate that is in limited supply. In apparent competition (4) the two populations affect each others' growth via a shared predator rather than a shared resource. Other schemes have been proposed where populations affect each other directly or indirectly via populations on the same trophic level (5). It is useful to be precise about which type of process is envisaged when competition is invoked. Because such a formalism already exists in the ecological literature, it makes sense to adapt it to the special situation of cells competing within an organism. To go further and ask ''does the formalism fit the data?'' it becomes necessary to express the formal model in mathematical equations and see if those equations behave like the populations that we observe. This is the strategy we have adopted in the work presented here. We have developed formal schemes for competition among B lymphocytes that give rise to two models; one of competition in its broadest sense and one that is specifically a model of resource competition. We show detailed comparisons of our first model with our data on B lymphocyte population dynamic...

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Every year, up to 90,000 new cases of Visceral Leishmaniasis and 30,000 resultant deaths are estimated to occur worldwide. Such numbers give relevance to the continuous study of this complex form of the disease: a zoonosis and an anthroponosis; two known etiological agents ( Leishmania infantum and L. donovani , respectively); with an estimated average ratio of 1 symptomatic per 10 asymptomatic individuals; and sometimes associated with atypical clinical presentations. This complexity, which results from a long co-evolutionary process involving vector-host, host-pathogen, and pathogen-vector interactions, is still not completely understood. The determinants of visceralization are not fully defined and the dichotomy resistance vs. susceptibility remains unsolved, translating into obstacles that delay the progress of global disease control. Inbred mouse models, with different susceptibility patterns to Leishmania infection, have been very useful in exploring this dichotomy. BALB/c and C57BL/6 mice were described as susceptible strains to L. donovani visceral infection, while SV/129 was considered resistant. Here, we used these three mouse models, but in the context of L. infantum infection, the other Leishmania species that cause visceral disease in humans, and dynamically compared their local and systemic infection-induced immune responses in order to establish a parallel and to ultimately better understand susceptibility vs. resistance in visceral leishmaniasis. Overall, our results suggest that C57BL/6 mice develop an intermediate “infection-phenotype” in comparison to BALB/c and SV/129 mouse strains, considering both the splenic parasite burden and the determined target organs weights. However, the immune mechanisms associated with the control of infection seem to be different in each mouse strain. We observed that both BALB/c and SV/129, but not C57BL/6 mice, show an infection-induced increase of splenic T follicular helper cells. On the other hand, differences detected in terms of CD21 expression by B cells early after infection, together with the quantified anti- Leishmania specific antibodies, suggest that SV/129 are faster than BALB/c and C57BL/6 mice in the assembly of an efficient B-cell response. Additionally, we observed an infection-induced increase in polyfunctional CD4+ T cells in the resistant SV/129 model, opposing an infection-induced increase in CD4+IL-10+ cells in susceptible BALB/c mice. Our data aligns with the observations reported for L. donovani infection and suggest that not only a single mechanism, but an interaction of several could be necessary for the control of this parasitic disease.

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The hemodynamic parameters evaluated in third molar surgery with 2% lidocaine and 4% articaine (both with epinephrine 1:100,000) did not show significant differences.

A rare case of fracture of the coronoid and the pterygoid process caused by firearms is described. A 28-year-old male was hit by a bullet in the face, resulting in restricted mouth opening, difficulty in chewing and pain when opening the mouth. Clinical examination revealed a perforating wound in the right parotid region and a similar wound on the left side of the same region. A CT scan showed comminuted fracture of the left coronoid process and bilateral comminuted fracture of the pterygoid processes. Treatment was conservative, speech therapy was conducted and it was successful. Details of the clinical signs, radiology (3D-CT scan), treatment and follow-up are presented.