Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans.

BackgroundThe closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation.MethodsSecretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum.ResultsMost measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate.ConclusionsWe show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0907-5) contains supplementary material, which is available to authorized users.

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