T-dependent Ab responses are characterized by parallel extrafollicular plasmablast growth and germinal center (GC) formation. This study identifies that, in mice, the Ab response against Salmonella is novel in its kinetics and its regulation. It demonstrates that viable, attenuated Salmonella induce a massive early T-dependent extrafollicular response, whereas GC formation is delayed until 1 mo after infection. The extrafollicular Ab response with switching to IgG2c, the IgG2a equivalent in C57BL/6 mice, is well established by day 3 and persists through 5 wk. Switching is strongly T dependent, and the outer membrane proteins are shown to be major targets of the early switched IgG2c response, whereas flagellin and LPS are not. GC responses are associated with affinity maturation of IgG2c, and their induction is associated with bacterial burden because GC could be induced earlier by treating with antibiotics. Clearance of these bacteria is not a consequence of high-affinity Ab production, for clearance occurs equally in CD154-deficient mice, which do not develop GC, and wild-type mice. Nevertheless, transferred low- and high-affinity IgG2c and less efficiently IgM were shown to impede Salmonella colonization of splenic macrophages. Furthermore, Ab induced during the infection markedly reduces bacteremia. Thus, although Ab does not prevent the progress of established splenic infection, it can prevent primary infection and impedes secondary hemogenous spread of the disease. These results may explain why attenuated Salmonella-induced B cell responses are protective in secondary, but not primary infections.

Charnley [1] developed the first bone cement in the 1960s using poly(methyl methacrylate) (PMMA), which remains the most widely used material for fixation of orthopaedic joint replacements. In the field of dentistry, zinc polycarboxylate and glass polyalkenoate cements received major research interest from the 1970s to the present day. The discovery of a well-integrated intermediate layer between bone and many bioactive ceramic phases from the calcium-phosphate system, such as hydroxyapatite (HA), resulted in the development of new cements incorporating such phases. These investigations ranged from the development of castable bioactive materials to modified bioactive composites. This paper attempts to give a broad overview of the many different types of cements that have being developed in the past and those which are being researched at the present time. It has lead to a set of fundamental design criteria that should be considered prior to the development of a cement for use as a bone cement or in applications requiring a bone substitute.

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