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How can APC cells become autoreactiv against own antigens if they only have PRR as recognition complexes - and are not under central/peripheral immune tolerance?

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This question is very concise and does not offer any further explanations. Two ways to understand the question can be set apart:

A. Question is on ambiguity of the expression "autoreactive APC cells".

B. Question inquires about theories on APCs in contrast to T- and B-cells becoming autoreactive.

A. Ambiguity of the term "autoreactive APCs"

The question does not refer to any source on "autoreactive APC" and a google search for this expression does not seem to offer any valid results. Please add reference.

Bing search "apc cells autoreactive" brought up, first entries:

(1.) Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis

(2.) "These experiments suggest that B cells are the predominant APC responsible in the activation of autoreactive T cells..."

Google searching, moreover, brought up:

(3.) Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection

Clearly, with Bing's quoted results, there are the APCs on one side, and the autoreactive T-cells on the other side which reflects the basic mechanism of immunization: APCs present antigen to T- and B-lymphcytes which only then become reactive; left naive and unprimed they cannot be either reactive against foreign nor self antigen, but remain anergic. Thus, according to basic knowledge, for every autoreactive T- or B-cell there exist their correponding priming/activating APC. Any APC cell that activated may thus be named "autoreactive APC"; and those APCs do not use t-/b receptor but its ligand, and they are not "under immune tolerance" as they activate and are not passively activated. As the APCs induce autoreactivity on the side of their partners, the T- (or B) lymphocytes, they "become" and may be called "autoreactive" in a derivative sense.

As google result Nr.3 suggests, there may be texts and search results where it is less evident that "autoreactive APCs" just refers to the corresponding priming APCs of the autoreactive T- and B-cells in question. On the other hand, one quote from result Nr.3 may help to explain some basics underlying the question: "...we show that autoreactive thymic B cells serve as efficient antigen-presenting cells for T cell negative selection...". That may translate into asking: How can B-cells, that count among the APC, "become autoreactive" if they never have acquired tolerance because they never have been primed but (only) negatively select T-cells producing tolerance? They have "nothing to lose". At the same time, the fact that, different from dendritic cells and macrophages, the B cells do not have the PRR alludeds to the intricacy the question bears (have they been primed themselves - if yes, what about other APCs).

This said, should the question translate to asking how APCs can be called autoreactive in spite of them not getting selected by the priming process the answer is: because for every autoreactive lymphocyte there is a corresponding APC that did the activation, the priming and the negative selection inducing tolerance that vained. For this role, no hindrance in having only the PRR (as it is the APCs ligand to T-/B-cell receptors that does the activation).

I hope this answer is based on a correctly detected basic level of this interesting question (hope to have shown the intricacy, at the same time).

B. Theories on APCs in contrast to T- and B-cells becoming autoreactive

The question mentions "PRR". With any receptor, there is a ligand, and PRR is not the ligand of TCR/BCR. To paraphrase the question in some informal way: Can APCs become autoreactive because, different from autoreactive t- and b-cells, they have the PRR receptor? Refering to the above: Is there autoreactivity of APCs that is not only derived from their binding to the t- and b-cell receptor of selected autoreactive lymphycytes but is based on - for instance mutational - changes of their PRR, pattern recognition receptors? How can APCs, the antigen presenting cells, become auto-immune/autoreactive by mechanisms that do not depend on t-/b-cell receptor or ligands usage as they only feature the PRR? How can APCs become autoreactive themselves? Do they take take up self antigen via PRR to induce self-immunity? Or is auto-immunity nothing more than a loss of tolerance of t-/b- cells?

See Wikipedia on Central tolerance:

"In the human immune system, central tolerance (also known as negative selection) is the process of eliminating any developing T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides" (...) "Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs."

The quoted text and others do not elaborate on the mechanisms of auto-immunity as they are still unclear, and in that context, on the referenced page for instance, the APC cells your question focuses on are not even being mentioned.

Hence, it seems that auto-immunity is some loss of something acquired - tolerance. Once a T- or B-lymphocyte has undergone the process of acquiring tolerance (is "under central/peripheral immune tolerance") it may lose that tolerance, by way of mutation for instance. If t- and b-cell receptors are prerequisites for acquisition, then loss, can APCs which do not have those receptors, but have the PRR, undergo similar changes on their side?

See Wikipedia on Autoimmunity:

"Pioneering work by Noel Rose and Ernst Witebsky in New York, and Roitt and Doniach at University College London provided clear evidence that, at least in terms of antibody-producing B cells (B lymphocytes), diseases such as rheumatoid arthritis and thyrotoxicosis are associated with loss of immunological tolerance, which is the ability of an individual to ignore "self", while reacting to "non-self". This breakage leads to the immune system's mounting an effective and specific immune response against self antigens. The exact genesis of immunological tolerance is still elusive, but several theories have been proposed..."

On common theories about the origins of auto-immunity, see Wikipedia, Autoimmunity/Genetic factors:

"The contributions of genes outside the MHC complex remain the subject of research", PRR not being mentioned.

See also, for some other example,:

(Schaumburg et al., search result No.1) "Studies focused on defining the influence of inflammatory stimuli on activation of different APC subsets and how these subsets direct activation and differentiation of pathogenic lymphocytes will be valuable in developing a greater understanding of the complex mechanisms orchestrating the immunopathogenesis of dry eye disease."

This speaks in favour of causes for APC cells to induce or maintain autoreactivity of lymphocytes not being known yet. That study, for instance, tries to show that it is not only a loss of tolerance on the side of already primed and selected lymphocytes that is cause of auto-immunity. This quote at the same time illustrates that "loss of tolerance gained" is a valid concept which indeed questions any active role of APCs in auto-immunity (as the question appears to assume).

Edit: Further search finally brought up reference on how APC cells can become autoreactive, in spite of themselves not being under immune tolerance, see

Travis et al., Nature 2007, "Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice: "... Here we show that conditional loss of the TGF-beta-activating integrin alpha(v)beta8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha(v)beta8 on dendritic cells, (...) These results suggest that alpha(v)beta8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha(v)beta8 on dendritic cells to induce and/or maintain tissue T(R) cells."

This study found causes for auto-reactivity of lymphocytes in "lack of alpha(v)beta8" protein on membranes of APC, i.e. causes that are independent from "PRR as recognition complexes" and the immune tolerance inducing process of "central/peripheral immune tolerance".

See also the links at the end of the answer to a related question. The concept of "autoreactive APCs" as causing auto-immunity can hardly be found.

Hence:

There seem to be findings on APCs becoming autoreactive by way of cell recognition and signalling outside the MHC, making use of membrane proteins that are different form PRR or T-/B-cell receptors and do not regard central/peripheral immune tolerance in the strict sense of positive and negative selection.

There is still more to it, please allow to elaborate:

The B cells mentioned in first quotes above count among the APCs; the B cell acts as APC when it presents antigen to T-helper cells. And, much lesser known, B cells can be activated by other APCs, by dendritic cells, that present antigen to to b cells. The Wikipedia page refered to above says: "Properly functioning B cell receptors recognize non-self antigen, or pathogen-associated molecular proteins (PAMPs)."

The B cell receptor, known for "specifity" and "under central/peripheral immune tolerance" may, in my opinion and as the question alludes, be tentatively be considered a PRR, possibly receiving signals that are "unspecific" in respect of the concept of auto-immunity. B cells are known to change the specifity of their anti-bodies (refining them in the course of cell divisions). The B cells (in contrast to T cells) in spite of being selected in their role as lymphocytes might uptake and present to T4-cells self-antigen they had been ignorant to before.

In that context, Wikipedia intriguingly states (page linked above, on Autoimmunity):

"A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely restricted to the autoantibody responses produced by B lymphocytes. Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell response it is usually not to the antigen recognised by autoantibodies." Having understood that your question unintentionally alludes to some double functionality of the b-cells, the question thus offers some new look at the causes of auto-immunity.

B cells - considered APCs - do not have the PRR, and must be excluded from the APCs the question refers to (as they do not have the PRR, thus leaving only macrophages and dendritic cells refered to by "APC cells").

Highlighting in quotes by the author.

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